首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   335篇
  免费   9篇
  国内免费   9篇
  353篇
  2022年   1篇
  2020年   7篇
  2019年   4篇
  2018年   3篇
  2017年   5篇
  2016年   3篇
  2015年   5篇
  2014年   11篇
  2013年   33篇
  2012年   11篇
  2011年   21篇
  2010年   15篇
  2009年   17篇
  2008年   27篇
  2007年   19篇
  2006年   19篇
  2005年   19篇
  2004年   14篇
  2003年   18篇
  2002年   8篇
  2001年   3篇
  2000年   4篇
  1999年   5篇
  1998年   2篇
  1997年   7篇
  1996年   7篇
  1995年   4篇
  1994年   7篇
  1993年   6篇
  1992年   4篇
  1991年   6篇
  1989年   1篇
  1988年   4篇
  1987年   2篇
  1986年   1篇
  1985年   3篇
  1984年   1篇
  1983年   4篇
  1982年   7篇
  1981年   9篇
  1980年   5篇
  1979年   1篇
排序方式: 共有353条查询结果,搜索用时 15 毫秒
1.
    
A series of cellular-automata (CA) models have been created, simulating relationships between water (or aqueous solutions) and solid surfaces of differing hydropathic (i.e., hydrophilic or hydrophobic) nature. Both equilibrium- and dynamic-flow models were examined, employing simple breaking and joining rules to simulate the hydropathic interactions. The CA simulations show that water accumulates near hydrophilic surfaces and avoids hydrophobic surfaces, forming concave-up and concave-down meniscuses, resp., under equilibrium conditions. In the dynamic-flow simulations, the flow rate of water was found to increase past a wall surface as the surface became less hydrophilic, reaching a maximum rate when the solid surface was of intermediate hydropathic state, and then declining with further increase in the hydrophobicity of the surface. Solution simulations show that non-polar solutes tend to achieve higher concentrations near hydrophobic-wall surfaces, whereas other hydrophobic/hydrophilic combinations of solutes and surfaces do not show such accumulations. Physical interpretations of the results are presented, as are some possible biological consequences.  相似文献   
2.
Recombinant human interferon-beta (β-IFN), used in the therapeutic treatment of multiple sclerosis (MS), can be produced on a large-scale from genetically engineered Chinese hamster ovary (CHO) cells. However, its hydrophobicity causes non-reversible, molecular aggregation in culture. The parameters affecting aggregation were determined to be concentration, culture residence time, temperature and glycosylation. Although the protein can be produced in Escherichia coli in a non-glycosylated form, the addition of glycans confers a reduced rate of aggregation as well as a 10-fold higher bioactivity. We report on the application of a low temperature perfusion culture designed to control the parameters that cause aggregation. In this three-phase culture system there is a transition to a low temperature (32°C) in a batch mode prior to implementing perfusion at 1 volume/day using an acoustic cell separator. Perfusion at the low temperature resulted in a 3.5-fold increase in specific productivity and a 7-fold increase in volumetric productivity compared to the batch culture at 37°C. The percentage aggregation of β-IFN was reduced from a maximum of 43% in batch culture to a minimum of 5% toward the end of the perfusion phase. The glycosylation profile of all samples showed predominantly sialylated biantennary fucosylated structures. The extent of sialylation, which is important for bioactivity, was enhanced significantly in the perfusion culture, compared to the batch culture.  相似文献   
3.
    
Interaction of macromolecules in aqueous salt‐containing solution with a hydrophobic adsorbent is studied by adsorption equilibrium measurements and by independent isothermal titration calorimetry. The macromolecules are native as well as mono‐, di‐, and tri‐PEGylated lysozyme and four pure PEGs. The hydrophobic adsorbent is Toyopearl PPG‐600M. The salt is sodium chloride. The sodium chloride concentration in the aqueous 25 mM sodium phosphate buffer is varied from 2000 to 4500 mM at pH 7.0 and 25°C. PEGylation of the lysozyme is carried using 5 and 10 kDa PEG chains. The molar enthalpy of adsorption is calculated from the adsorption equilibrium and the calorimetric data. The results show that the adsorption of the PEGylated lysozyme is caused by both the interaction of the lysozyme and the interaction of the PEG chains with the adsorbent, respectively, but the interaction of the lysozyme is stronger than that of PEG. The comparison of the results of the present study on the influence of sodium chloride with a corresponding study on the influence of ammonium sulfate shows that the adsorption mechanism changes upon the variation of the salt. The knowledge of the adsorption mechanisms supports the systematic development of chromatographic purification steps.  相似文献   
4.
Abstract

In this study, various molecular dynamics simulations were conducted to investigate the effects of ethanol and temperature on the conformational changes of human lysozyme, which may lead insights into amyloidosis. The analyses of some important structural characteristics, such as backbone root-mean-square deviation, secondary structural stability, radius of gyration, accessible surface area, and hydrophobic contact of the hydrophobic core all show that ethanol tends to destabilize human lysozyme at high temperatures. It can be attributed to that higher temperatures result in the destruction of the native structure of this protein, leading to the exposure of the interior hydrophobic core. At this stage, ethanol plays a role to destroy this region by forming hydrophobic interactions between protein and solvent due to its lower polarity comparing to water. Such newly formed intermolecular interactions accelerate the unfolding of this protein, starting from the core between the a- and β-domains. Our results are in good agreement with the previous hypothesis suggesting that the distortion of the hydrophobic core at the α- and β-interface putatively results in the formation of the initial “seed” for amyloid fibril. Although the present results cannot directly be linked to fibril formation, they still provide valuable insights into amyloidosis of human lysozyme.  相似文献   
5.
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC50 values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Ki value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.  相似文献   
6.
Peter R. Rich 《BBA》1981,637(1):28-33
The pathways of redox equilibration of quinols and quinones have been investigated. The rate-limiting reaction involves the couple QH?/QH· of the reducing quinol and the couple Q?/Q of the oxidising quinone. Three general mechanistic points may be surmised: (i) protonation/deprotonation reactions are not rate-limiting; (ii) all transfers occur in one-equivalent steps; (iii) electron transfers, but not hydrogen atom transfers, are the dominant features. In aprotic media, no rapid route of equilibration is available since the ionic species which are necessary for thermodynamically feasible routes of electron transfer cannot exist to any great extent. The relation of these results to models of biological quinone systems is discussed.  相似文献   
7.
A spectroscopic examination of six galactonoamidines with inhibition constants and efficacy in the low nanomolar concentration range (Ki = 6–11 nM, IC50 = 12–36 nM) suggested only two of them as putative transition state analogs for the hydrolysis of β-galactosides by β-galactosidase (A. oryzae). A rationale for the experimental results was elaborated using docking and molecular dynamics studies. An analysis of the combined observations reveals several common factors of the compounds suggested as transition state analogs (TSAs): the putative TSAs have a similar orientation in the active site; show conserved positioning of the glycon; display a large number of H-bond interactions toward the catalytically active amino acid residues via their glycon; and exhibit hydrophobic interactions at the outer rim of the active site with small changes of the position and orientation of their respective aglycons.  相似文献   
8.
基于HP模型的蛋白质折叠问题的研究   总被引:1,自引:0,他引:1  
史小红 《生物信息学》2016,14(2):112-116
基于蛋白质二维HP模型提出改进的遗传算法对真实蛋白质进行计算机折叠模拟。结果显示疏水能量函数最小值的蛋白质构象对应含疏水核心的稳定结构,疏水作用在蛋白质折叠中起主要作用。研究表明二维HP模型在蛋白质折叠研究中是可行的和有效的并为进一步揭示蛋白质折叠机理提供重要参考信息。  相似文献   
9.
The adsorption of nonionic surfactants on hide powder previously treated with anionic surfactants has been studied. The adsorption of nonionic surfactants takes place through hydrophobic interactions. A mechanism has been proposed for this interaction, assuming that the nonionic surfactant has been fixed by means of secondary adsorption (hydrophobic interaction) after the primary adsorption of the anionic surfactant (ionic and hydrophobic interaction) which makes it possible.  相似文献   
10.
秦岭地区玉竹根茎的脂溶性成分及其抑菌活性研究   总被引:3,自引:0,他引:3  
从秦岭产玉竹(Polygonatum odoratum)根茎的石油醚萃取物中分离得到8个化合物,其中有5个化合物为首次从黄精属植物中得到,其结构分别为:(1)(24R/S)-9,19-环阿尔廷-25-烯-3β,24-二醇;(2)α-棕榈酸甘油酯;(3)棕榈酸甲酯;(4)二十八碳酸;(5)(Z)-6-十九碳烯酸。首次对化合物1的抗菌活性进行了测定,发现化合物1在浓度为10μg/mL时,对黄瓜炭疽病原菌的抑制率达到100%;在浓度为100μg/mL时,对灵杆菌的抑菌能力与红霉素相当。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号