全文获取类型
收费全文 | 315篇 |
免费 | 46篇 |
专业分类
361篇 |
出版年
2015年 | 7篇 |
2014年 | 10篇 |
2013年 | 33篇 |
2012年 | 10篇 |
2011年 | 10篇 |
2010年 | 8篇 |
2009年 | 14篇 |
2008年 | 14篇 |
2007年 | 15篇 |
2006年 | 7篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 9篇 |
2001年 | 6篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1971年 | 3篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1943年 | 2篇 |
1915年 | 2篇 |
1897年 | 2篇 |
1883年 | 3篇 |
1882年 | 5篇 |
1881年 | 2篇 |
1879年 | 6篇 |
1878年 | 2篇 |
1877年 | 2篇 |
排序方式: 共有361条查询结果,搜索用时 15 毫秒
291.
292.
293.
294.
295.
Dysregulation of copper and zinc homeostasis in the brain plays a critical role in Alzheimer disease (AD). Copper binding to amyloid-beta peptide (Abeta) is linked with the neurotoxicity of Abeta and free radical damage. Metallothionein-3 (MT-3) is a small cysteine- and metal-rich protein expressed in the brain and found down-regulated in AD. This protein occurs intra- and extracellularly, and it plays an important role in the metabolism of zinc and copper. In cell cultures Zn7MT-3, by an unknown mechanism, protects neurons from the toxicity of Abeta. We have, therefore, used a range of complementary spectroscopic and biochemical methods to characterize the interaction of Zn7MT-3 with free Cu2+ ions. We show that Zn7MT-3 scavenges free Cu2+ ions through their reduction to Cu+ and binding to the protein. In this reaction thiolate ligands are oxidized to disulfides concomitant with Zn2+ release. The binding of the first four Cu2+ is cooperative forming a Cu(I)4-thiolate cluster in the N-terminal domain of Cu4,Zn4MT-3 together with two disulfides bonds. The Cu4-thiolate cluster exhibits an unusual stability toward air oxygen. The results of UV-visible, CD, and Cu(I) phosphorescence at 77 K suggest the existence of metal-metal interactions in this cluster. We have demonstrated that Zn7MT-3 in the presence of ascorbate completely quenches the copper-catalyzed hydroxyl radical (OH.) production. Thus, zinc-thiolate clusters in Zn7MT-3 can efficiently silence the redox-active free Cu2+ ions. The biological implication of our studies as to the protective role of Zn7MT-3 from the Cu2+ toxicity in AD and other neurodegenerative disorders is discussed. 相似文献
296.
Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor 总被引:3,自引:0,他引:3
Heparin depresses the second-order rate constant ka for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases ka from 1.3 x 10(7) M-1 s-1 to a limit of 4.6 x 10(4) M-1 s-1. Low molecular mass heparin is about 7-fold less effective. Dermatan sulfate and chondroitin sulfate are less efficient. Heparin preparations used in clinical care also strongly depress ka when tested at concentrations corresponding to their clinical efficacy. Heparin also decreases the ka for the elastase/eglin c and the cathepsin G/alpha 1-proteinase inhibitor systems but not that for the alpha 1-proteinase inhibitor/pancreatic elastase or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate that the ka-depressing effect of the polymer is related to its ability to form a tight complex with elastase but not with alpha 1-proteinase inhibitor. One mol of high molecular mass heparin binds 3 mol of neutrophil elastase with a Kd of 3.3 nM. Low molecular mass heparin binds elastase with a 1:1 stoichiometry and a Kd of 89 nM. For both heparins ka is lowest when elastase is fully saturated with heparin. From this we conclude that heparin decreases ka, because the heparin-elastase complex is able to slowly react with alpha 1-proteinase inhibitor and not because the inhibitor slowly dissociates the heparin-elastase complex. These findings may have important pathophysiological bearing. 相似文献
297.
298.
Stefan Richter Rudi Loesel Günter Purschke Andreas Schmidt-Rhaesa Gerhard Scholtz Thomas Stach Lars Vogt Andreas Wanninger Georg Brenneis Carmen Döring Simone Faller Martin Fritsch Peter Grobe Carsten M Heuer Sabrina Kaul Ole S Møller Carsten HG Müller Verena Rieger Birgen H Rothe Martin EJ Stegner Steffen Harzsch 《Frontiers in zoology》2010,7(1):1-49
299.
300.
Increased expression of CD4 molecules on Jurkat cells mediated by human immunodeficiency virus tat protein. 下载免费PDF全文
P Koka J Yunis A L Passarelli D P Dubey D V Faller E J Ynis 《Journal of virology》1988,62(11):4353-4357
The tat gene of the human immunodeficiency virus, tat-III, when introduced into T-lymphoblastoid Jurkat cells by a Moloney retroviral recombinant DNA vector expressed high levels of the functional tat protein as measured by the chloramphenicol acetyltransferase assay. Immunofluorescence analysis with CD4-specific monoclonal antibodies demonstrated that the cell surface levels of the CD4 antigen were increased by 5- to 10-fold in the tat-III-infected Jurkat cells. Cellular cytoplasmic RNA analysis indicated that the enhanced CD4 expression was mediated at the mRNA level. Our findings suggest that the single expression of the human immunodeficiency virus tat protein in the absence of the other viral proteins causes an upregulation of CD4 gene expression on helper T cells, although infection of these cells by the virus, thus expressing all the viral gene products including tat, is known to downregulate CD4 antigen expression. 相似文献