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Synthesis, Characterizations, Biological, and Molecular Docking Studies of Some Amino Acid Schiff Bases with Their Cobalt(II) Complexes 一些氨基酸席夫碱及其钴(II)配合物的合成、表征、生物学和分子对接研究
Pub Date : 2017-09-22 DOI: 10.4236/ABC.2017.75013
M. Salama, Soad Ahmed, Safaa S. Hassan
The synthesis and structural characterization of cobalt(II) complexes of amino acid Schiff bases was prepared from Salicylaldehyde and three amino acid (Valine, Leucine, and Isoleucine) in basic medium. The metal complexes was synthesized by treating an ethanolic solution of the ligand with appropriate amount of metal salts [1:2] [M:L] ratio. The synthesized Schiff bases and their metal complexes have been investigated on the bases of elemental chemical analysis, FTIR, electronic spectral, 1HNMR, 13CNMR, MS, molar conductance and magnetic susceptibility measurements. The electronic spectra of the metal complexes and their magnetic susceptibility measurements suggest octahedral structures are the probable coordination geometries for the isolated complexes. The Schiff bases and their metal complexes were preliminary scanned against various strains of microbes to study their biological effect.
以水杨醛和三种氨基酸(缬氨酸、亮氨酸和异亮氨酸)为原料,在碱性介质中制备了氨基酸席夫碱配合物钴(II)的合成和结构表征。在配体的乙醇溶液中加入适量的金属盐[1:2][M:L],合成金属配合物。通过元素化学分析、FTIR、电子光谱、1HNMR、13CNMR、MS、摩尔电导和磁化率等手段对合成的席夫碱及其金属配合物进行了表征。金属配合物的电子能谱及其磁化率测量表明,八面体结构可能是分离配合物的配位几何形状。对希夫碱及其金属配合物进行了针对不同微生物菌株的初步扫描,研究了其生物学效应。
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引用次数: 10
Re-Thinking Biology—I. Maxwell’s Demon and the Spontaneous Origin of Life 反思上学期。麦克斯韦妖与生命的自发起源
Pub Date : 2017-09-22 DOI: 10.4236/ABC.2017.75012
C. Busby, C. Howard
A hypothesis is advanced in which life began from a Darwinian selection among a diversification of molecular species containing the phosphate moiety which broke the constraints implicit in the Second Law of Thermodynamics, discussed famously by Schrodinger, by obtaining energy from specific infrared frequencies located in the phosphorus-oxygen vibration at a frequency around 1000 cm-1. We propose the source of this energy was from the internal conversion of solar broadband energy by the phosphate mineral Apatite, present at the bottom of a primitive biogenesis pond. In this scenario, life is re-defined as being hotter than its environment and as using its excess energy, supplied by infra-red conversion, to react with its molecular environment and pump itself up the “entropy slope” thereby; replication is through breakages of increasingly large phosphate containing biopolymers. The idea has implications for modern explanations of living systems.
提出了一种假设,即生命始于达尔文式的选择,即在含有磷酸盐部分的分子物种的多样化中,通过从磷氧振动中的特定红外频率获得能量,打破了薛定谔著名讨论的热力学第二定律中隐含的约束,频率约为1000 cm-1。我们认为这种能量的来源是存在于原始生物发生池底部的磷酸盐矿物磷灰石对太阳能宽带能量的内部转换。在这种情况下,生命被重新定义为比环境更热,并利用红外转换提供的多余能量与分子环境反应,从而使自己上升到“熵斜率”;复制是通过破坏越来越大的含磷酸盐的生物聚合物。这一观点对现代生活系统的解释具有启示意义。
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引用次数: 1
Comparison of Serum Phospholipase A2 Activities of All Known Extant Crocodylian Species 所有已知现存鳄鱼种血清磷脂酶A2活性的比较
Pub Date : 2017-08-25 DOI: 10.4236/ABC.2017.74010
Mark Merchant, C. McAdon, S. Mead, Justin McFatter, C. McMahan, R. Griffith, Christopher M. Murray
Serum samples from all 23 extant crocodilian species were tested for phospholipase A2 (PLA2) activity against nine different bacterial species. The data were used to generate a PLA2 activity profile for each crocodilian species, and the data were used to compare the activities of the three main lineages (Alligatoridae, Crocodylidae, and Gavialidae), the seven different genera, and to compare all of the 23 individual species. The data revealed that the three lineages ofcrocodilians (Alligatoridae, Crocodylidae, and Gavialidae) exhibited PLA2 activities toward nine species of bacteria that were statistically distinguishable. In addition, the PLA2 activities of crocodilians in a specific genus tended to be more similar to other members in their genus than to members of other crocodilian genera.
对所有23种现存鳄鱼的血清样本进行了磷脂酶A2 (PLA2)对9种不同细菌的活性检测。这些数据被用于生成每个鳄鱼物种的PLA2活性谱,并用于比较三个主要谱系(短吻鳄科、鳄鱼科和大鳄科)7个不同属的活性,以及比较所有23个个体种的活性。数据显示,鳄鱼的三个谱系(短吻鳄科、鳄鱼科和鳄鱼科)对9种细菌具有统计学上可区分的PLA2活性。此外,特定属的鳄鱼的PLA2活性倾向于与其属的其他成员比其他鳄鱼属的成员更相似。
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引用次数: 1
Citrus jabara Extracts Suppress MUC5AC Mucin Production in Human Lung Epithelial Cells 柑桔提取物抑制人肺上皮细胞MUC5AC粘蛋白的产生
Pub Date : 2017-06-29 DOI: 10.4236/ABC.2017.73009
J. Iwashita, N. Iguchi, A. Takashima, Daisuke Watanabe, Kimihiko Sano, Masahiko Ishikuro, K. Hata, J. Murata
In the human airway, the overproduction of MUC5AC mucin is a key feature of allergic asthma, and it induces airway narrowing and obstruction. The production of MUC5AC is regulated by several signals, but the mechanism is not completely understood. We investigated the effect of jabara, a citrus containing abundant flavonoids, on the regulation of MUC5AC production. When NCI-H292 human airway epithelial cells were cultured with jabara extracts, we found that the expression of Periodic acid-schiff stained mucin was suppressed with downregulated MUC5AC production. In human primary airway cells derived from asthmatic patients, MUC5AC production was also suppressed by jabara extracts. The treatment of cells with jabara extracts decreased ERK activation in NCI-H292 and in primary cells. These results show that jabara extracts contain some factors that suppress MUC5AC production and ERK activity and suggest that it will be useful for relieving asthma.
在人类气道中,MUC5AC粘蛋白的过量产生是过敏性哮喘的一个关键特征,它会导致气道狭窄和阻塞。MUC5AC的产生受多种信号的调控,但其机制尚不完全清楚。研究了含丰富黄酮类化合物的柑桔贾巴拉对MUC5AC产生的调控作用。用天麻提取物培养NCI-H292人气道上皮细胞时,我们发现周期酸-希夫染色粘蛋白的表达受到抑制,MUC5AC的表达下调。在来源于哮喘患者的人原代气道细胞中,贾巴拉提取物也抑制MUC5AC的产生。用贾巴拉提取物处理细胞可降低NCI-H292和原代细胞中ERK的激活。这些结果表明,菝葜提取物中含有抑制MUC5AC产生和ERK活性的因子,提示其具有缓解哮喘的作用。
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引用次数: 4
Fc-Epsilon Receptor (CD23) Expressing Follicular Dendritic Cells as a Main Prognostic Factor in Follicular Lymphoma 表达滤泡树突状细胞的Fc-Epsilon受体(CD23)是滤泡性淋巴瘤的主要预后因素
Pub Date : 2017-04-25 DOI: 10.4236/ABC.2017.72007
N. Falaleeva, E. Osmanov, N. Tupitsyn
Fc-epsilon receptor (CD23)-expressing follicular dendritic cells is a main prognostic factor in follicular lymphoma. Falaleeva N. A., Osmanov E. A., Tupitsyn N. N. Federal State Budgetary Institute N. N. Blokhin Russian Cancer Research Center, Health Ministry of Russian Federation, Moscow, Russia SUMMARY Follicular dendritic cells, expressing FceRII or CD23 (FceRIIFDCs) as a component of non-tumor environment have been studied in 232 follicular lymphoma (FL) patients. FceRIIFDCs were found in 87.5% of follicular lymphoma cases and were associated with a nodular pattern of tumor growth (p = 0.000), but not the cytological grade of lymphoma. There were no associations of FceRIIFDC with clinical prognostic factors (FLIPI indices) or with bone marrow involvement in FL patients by histology. The presence of FceRIIFDCs in tumor tissue was an independent prognostic factor according to treatment results, i.e. frequency of CR, duration of OS and PFS. Bone marrow involvement significantly worsened the prognosis in FceRIIFDC-positive group of patients. We suggest a new prognostic index (FDC-IP) that allows biochemical identification of the following patient groups: FceRIIFDC-positive patients without bone marrow involvement (good prognosis), FceRIIF-DC-positive patients with bone marrow involvement (intermediate prognosis), FceRIIFDC-negative patients (poor prognosis). These 3 groups significantly differ (p = 0.000) both in OS and in PFS. This is the first evidence of the possibility to assess tumor behavior and treatment results in FL according to lymphoma biochemical and other than clinical parameters.
表达Fc-epsilon受体(CD23)的滤泡树突状细胞是滤泡性淋巴瘤的主要预后因素。Falaleeva N. A, Osmanov E. A, Tupitsyn N. N. N.俄罗斯联邦卫生部俄罗斯癌症研究中心总结:在232例滤泡性淋巴瘤(FL)患者中研究了表达FceRII或CD23 (FceRIIFDCs)的滤泡树突状细胞作为非肿瘤环境的组成部分。在87.5%的滤泡性淋巴瘤病例中发现fceriifdc,并与肿瘤生长的结节型相关(p = 0.000),但与淋巴瘤的细胞学分级无关。从组织学上看,FceRIIFDC与FL患者的临床预后因素(FLIPI指数)或骨髓受累没有关联。根据治疗结果,即CR频率、OS持续时间和PFS,肿瘤组织中fceriifdc的存在是一个独立的预后因素。fceriifdc阳性组患者骨髓受累显著恶化预后。我们提出了一种新的预后指标(FDC-IP),可以对以下患者组进行生化鉴定:无骨髓受累的fceriifdc阳性患者(预后良好),骨髓受累的fceriifdc阳性患者(预后中等),fceriifdc阴性患者(预后差)。3组的OS和PFS均有显著差异(p = 0.000)。这是根据淋巴瘤生化和其他临床参数评估FL肿瘤行为和治疗结果的可能性的第一个证据。
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引用次数: 0
Development and Applications of a Calmodulin-Based Fusion Protein System for the Expression and Purification of WW and Zinc Finger Modules. 基于钙调素的WW和锌指蛋白表达纯化融合蛋白体系的建立与应用。
Pub Date : 2017-04-25 DOI: 10.4236/ABC.2017.72006
Christopher G Toomey, D. Weiss, A. Chant, Megan M. Ackerman, B. Ahlers, Y. Lam, Christopher Ricciardi, D. Bourne, Christina M. Kraemer-Chant
Calmodulin from Homo sapiens is an α-helical calcium-binding protein that expresses to high levels in E. coli. When the N-terminus of a calmodulin variant is bound to Ca2+, it undergoes a conformational change, exposing hydrophobic pockets. This property can be utilized for purification purposes, as these pockets bind to phenyl sepharose resin with high affinity. Washing with EDTA chelates the Ca2+ ions from the protein, inducing a conformational change back to the more folded state and eluting the protein from the column. We describe herein the use of a protein expression and purification technique using the calmodulin variant and a short linker for proteolytic cleavage by the mutant NIa-Pro tobacco etch virus protease. We have shown this approach to be useful in obtaining purified quantities of various small proteins that could not be expressed using other methods, including high enough concentrations of a designed WW domain protein for NMR structural analysis. We have also obtained promising results on the usefulness of this procedure to express and purify zinc finger proteins without the addition of zinc ions or other cofactors.
来自智人的钙调素是一种在大肠杆菌中高水平表达的α-螺旋钙结合蛋白。当钙调素变体的N末端与Ca2+结合时,它会发生构象变化,暴露出疏水性口袋。这种性质可用于纯化目的,因为这些口袋以高亲和性与苯基琼脂糖树脂结合。用EDTA洗涤可以螯合蛋白质中的Ca2+离子,诱导构象变化回到更折叠的状态,并将蛋白质从柱中洗脱。我们在本文中描述了使用钙调素变体和短连接体的蛋白质表达和纯化技术通过突变体NIa Pro烟草蚀刻病毒蛋白酶进行蛋白水解切割的用途。我们已经证明,这种方法可用于获得纯化量的各种小蛋白,这些小蛋白不能使用其他方法表达,包括用于NMR结构分析的足够高浓度的设计WW结构域蛋白。我们还获得了关于该程序在不添加锌离子或其他辅因子的情况下表达和纯化锌指蛋白的有用性的有希望的结果。
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引用次数: 0
Physico-Chemical and Microbiological Analysis of Water of the “Presa De Los Patos” in the Desierto De Los Leones National Park, Mexico 墨西哥Desierto De Los Leones国家公园“Presa De Los Patos”水体的理化和微生物学分析
Pub Date : 2017-04-25 DOI: 10.4236/ABC.2017.72008
Luis Raúl Gutiérrez-Lucas, Luz María Chávez-Ramírez, L. Arregui
The Desierto de los Leones National Park is a place that features recreational activities for residents and visitors to Mexico City. The Presa de los Patos (Ducks Dam) is one of the many bodies of water that are present in the park. By means of physico-chemical and microbiological analysis, it was determined that the water of the Presa de los Patos cannot be considered potable. The pH range was between 5.5 - 5.9. The turbidity exceeded the values established in the standards (10.7 - 32.3 Nephelometric Turbidity Units (NTU’s)). Chemical Oxygen Demand (COD) showed that large amounts of oxygen are needed to oxidize organic matter (106 - 450 mg/L). The amount of coliforms and fecal coliforms exceeds the values established by the standards used (total coliforms 98 - 956 Colony Forming Units (CFU’s), fecal coliforms 78 - 807 CFU’s). Five bacterial genera (Escherichia coli, Pseudomona, Klebsiella, Shigella and Salmonella) were isolated and identified. Most of the bacteria isolated were resistant to ampicillin (90%), while 25% were resistant to ciprofloxacin. The water consumption of the Presa de los Patos is a great risk for the habitants and visitors of the park.
Desierto de los Leones国家公园为墨西哥城的居民和游客提供娱乐活动。Presa de los Patos(鸭子坝)是公园中众多水体之一。通过物理化学和微生物分析,确定帕托斯河的水不能被视为饮用水。pH值范围在5.5-5.9之间。浊度超过了标准中规定的值(10.7-32.3浊度单位(NTU))。化学需氧量(COD)表明,氧化有机物需要大量的氧气(106-450mg/L)。大肠菌群和粪便大肠菌群的数量超过了所用标准规定的值(总大肠菌群98-956菌落形成单位(CFU),粪便大肠杆菌群78-807 CFU)。分离鉴定出大肠杆菌属、假单胞菌属、克雷伯菌属、志贺菌属和沙门氏菌属5个菌属。大多数分离的细菌对氨苄青霉素具有耐药性(90%),而25%的细菌对环丙沙星具有耐药性。Presa de los Patos的用水量对公园的居民和游客来说是一个巨大的风险。
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引用次数: 5
A Thiazole Analogue Exhibits an Anti-Proliferative Effect in Different Human Carcinoma Cell Lines and Its Mechanism Based on Molecular Modeling 一种噻唑类似物在不同人类癌细胞系中表现出抗增殖作用及其基于分子模型的机制
Pub Date : 2017-02-08 DOI: 10.4236/ABC.2017.71005
Hatem K. Amin, Amr M. El-Araby, Sameh Eid, T. Nasr, S. Bondock, O. Leheta, M. Dawoud
Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.
目的:研究噻唑类似物(5-乙酰基-4-甲基-2-(3-吡啶基)噻唑)对不同人癌细胞的增殖作用,并通过分子模型探讨其可能的作用机制。方法:采用肝癌(HEPG2)、乳腺腺癌(MCF7)和结肠癌(HCT116) 3种不同的人肝癌细胞系。对所测试的噻唑类似物及其虚拟类似物对细胞色素P-450 2A6酶和突变SOD进行了分子对接模拟。结果:细胞系细胞毒性实验表明,噻唑类似物对所有人肝癌细胞系均有明显的抗增殖活性,对肝癌细胞系HEPG2具有明显的抗增殖作用(IC50 = 23.8 μg/ml),对结肠癌细胞系和乳腺癌细胞系的抗增殖作用较差,IC50 = 50 μg/ml, IC50 = > 50 μg/ml。推测的作用机制显示其对肝脏中SOD和CYP2A6酶具有高亲和力。结论:噻唑类似物(5-乙酰基-4-甲基-2-(3-吡啶基)噻唑)是一种潜在的肝脏特异性抗癌药物,既能干扰肝脏细胞凋亡信号通路,又能干扰肝脏自由基加工,值得从不同角度对肝癌进行更多的研究,而不是凋亡信号通路。
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引用次数: 7
Mitochondrial Membranes Restitution Proceeds via Vesicular Import from ER and Cytosol. Counterparts’ Resemblances and Variances in Mitochondria and Golgi Pathways 线粒体膜的恢复通过内质网和细胞质的水泡输入进行。线粒体和高尔基体通路的异同
Pub Date : 2017-02-08 DOI: 10.4236/ABC.2017.71001
A. Slomiany, B. Slomiany
The processes of mitochondrial restitution are controlled by nuclear genes that encode proteins synthesized in ER and cytosol and delivered as organelle- and membrane-specific transport vesicles. The analysis of the transporters recovered from inner mitochondrial space (Mitosol) revealed that the ER-synthesized mitochondria-specific transport vesicles consist of two carriers, one remaining in outer mitochondrial membrane (OMM), and the other that transfers specific membrane segments to the inner mitochondrial membrane (IMM). The ER-assembled and IMM-committed membrane segments, while first integrated into OMM, undergo intra-mitochondrial lipid modification reflected in the synthesis of cardiolipin (CL) and inversion into Mitosol with load of IMM associated cytosolic proteins. Then, the CL-bedecked vesicles are released from OMM to Mitosol and upon contact with IMM fuse with the membrane, and the release of cytosolic cargo ensues. While ER-assembled mitochondria-specific transport vesicles fuse with OMM with the aid of the cytosolic, phosphatidylglycerol (PG)-specific phospholipase A2 (PLA2), the Mitosol-contained CL-specific PLA guides vesicles fusion with IMM. The described path of translocation of the membrane segments and the cytosol synthesized proteins into the designated mitochondrial compartments sustains growth and identity of OMM, IMM, maintains protein delivery for intra-mitochondrial lipid and protein modification in Mitosol, and ensures conformity of the cytosolic proteins cargo delivered to matrix.
线粒体恢复过程由核基因控制,核基因编码内质网和细胞质中合成的蛋白质,并作为细胞器和膜特异性运输囊泡传递。从线粒体内腔(Mitosol)中回收的转运蛋白分析表明,er合成的线粒体特异性转运囊泡由两个载体组成,一个留在线粒体外膜(OMM),另一个将特定的膜段转移到线粒体内膜(IMM)。er组装和IMM承诺的膜段首先整合到OMM中,经过线粒体内脂质修饰,反映在心磷脂(CL)的合成中,并在装载IMM相关的细胞质蛋白的情况下转化为线粒体。然后,包裹cl的囊泡从OMM释放到线粒体,与IMM接触后与膜融合,随后释放胞质货物。er组装的线粒体特异性运输囊泡在胞质磷脂酰甘油(PG)特异性磷脂酶A2 (PLA2)的帮助下与OMM融合,而含有线粒体的cl特异性PLA引导囊泡与IMM融合。所描述的将膜段和细胞质溶胶合成的蛋白质转运到指定的线粒体室的途径维持了OMM、IMM的生长和特性,维持了线粒体内脂质和线粒体中蛋白质修饰的蛋白质传递,并确保了传递到基质的细胞质蛋白质货物的一致性。
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引用次数: 3
Lipid-Protein Microinclusions in the Morphological Structures of Organelle Membranes Studied by Fluorescent Confocal Microscopy 荧光共聚焦显微镜研究细胞器膜形态结构中的脂质蛋白微包裹体
Pub Date : 2017-02-08 DOI: 10.4236/ABC.2017.71003
M. Chernyshov, V. Nurminsky, N. V. Ozolina
Peculiar properties of morphological structures of organelle membranes were studied by fluorescent confocal microscopy. The list of objects in our experiments was represented by mitochondria, chloroplasts and vacuoles. During this study, identification of lipid microinclusions having the form of such lipid-protein structural microformations as lipid-protein microdomains, vesicles and membrane tubular structures (cytoplasmic transvacuolar strands and nanotubes) located in organelle membranes or bound up with them was conducted. Such membrane probes as laurdan, DPH, ANS and bis-ANS were used. Comparison of fluorescence intensity of these membrane probes was conducted. This investigation of the morphological properties of lipid-protein structural microformations was accompanied with analysis of 1) the phase state and 2) dynamics of microviscosity variations in the membrane elements of isolated plant cell organelles. Distributions of laurdan fluorescence generalized polarization (GP) values for the membrane on the whole and for the intensively fluorescing membrane segments were obtained. It was discovered that the microviscosity of intensively fluorescing membrane segments essentially differed from the microviscosity of the rest part of the membrane. In conclusion, some results of the study of peculiar properties of lipid-protein structural microformations related to the structure of organelle membranes and the discoveries made in this investigation are discussed.
用荧光共聚焦显微镜研究了细胞器膜形态结构的特殊性质。我们的实验对象以线粒体、叶绿体和液泡为代表。在本研究中,鉴定了具有脂质-蛋白质结构微结构形式的脂质微内含物,如脂质-蛋白质微结构域、囊泡和膜管结构(细胞质跨液泡链和纳米管),这些结构位于细胞器膜上或与它们结合。采用laurdan、DPH、ANS、bis-ANS等膜探针。比较了这两种膜探针的荧光强度。对脂质-蛋白结构微形成形态特性的研究伴随着对分离植物细胞器膜元件的相态和微粘度变化动力学的分析。得到了膜整体和强荧光膜段的laurdan荧光广义偏振(GP)值的分布。研究发现,荧光强烈的膜段的微粘度与膜其余部分的微粘度有本质的不同。最后,讨论了与细胞器膜结构有关的脂质-蛋白结构微形成特性的一些研究结果和本研究的发现。
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引用次数: 2
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生物化学进展(英文)
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