全文获取类型
收费全文 | 179篇 |
免费 | 27篇 |
出版年
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 4篇 |
2012年 | 10篇 |
2011年 | 9篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 11篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1959年 | 1篇 |
1958年 | 1篇 |
1952年 | 1篇 |
1951年 | 1篇 |
1948年 | 3篇 |
1947年 | 4篇 |
1946年 | 1篇 |
1941年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有206条查询结果,搜索用时 15 毫秒
91.
92.
93.
94.
95.
Three New Species of the Genus Clostridium 总被引:3,自引:0,他引:3
Spray RS 《Journal of bacteriology》1948,55(6):839-842
96.
Structure-activity relations of the cardiac gap junction channel 总被引:14,自引:0,他引:14
97.
Mara R. N. Celes Lygia M. Malvestio Sylvia O. Suadicani Cibele M. Prado Maria J. Figueiredo Erica C. Campos Ana C. S. Freitas David C. Spray Herbert B. Tanowitz Jo?o S. da Silva Marcos A. Rossi 《PloS one》2013,8(7)
Sepsis, a major cause of morbidity/mortality in intensive care units worldwide, is commonly associated with cardiac dysfunction, which worsens the prognosis dramatically for patients. Although in recent years the concept of septic cardiomyopathy has evolved, the importance of myocardial structural alterations in sepsis has not been fully explored. This study offers novel and mechanistic data to clarify subcellular events that occur in the pathogenesis of septic cardiomyopathy and myocardial dysfunction in severe sepsis. Cultured neonatal mice cardiomyocytes subjected to serum obtained from mice with severe sepsis presented striking increment of [Ca2+]i and calpain-1 levels associated with decreased expression of dystrophin and disruption and derangement of F-actin filaments and cytoplasmic bleb formation. Severe sepsis induced in mice led to an increased expression of calpain-1 in cardiomyocytes. Moreover, decreased myocardial amounts of dystrophin, sarcomeric actin, and myosin heavy chain were observed in septic hearts associated with depressed cardiac contractile dysfunction and a very low survival rate. Actin and myosin from the sarcomere are first disassembled by calpain and then ubiquitinated and degraded by proteasome or sequestered inside specialized vacuoles called autophagosomes, delivered to the lysosome for degradation forming autophagolysosomes. Verapamil and dantrolene prevented the increase of calpain-1 levels and preserved dystrophin, actin, and myosin loss/reduction as well cardiac contractile dysfunction associated with strikingly improved survival rate. These abnormal parameters emerge as therapeutic targets, which modulation may provide beneficial effects on future vascular outcomes and mortality in sepsis. Further studies are needed to shed light on this mechanism, mainly regarding specific calpain inhibitors. 相似文献
98.
Fort AG Murray JW Dandachi N Davidson MW Dermietzel R Wolkoff AW Spray DC 《The Journal of biological chemistry》2011,286(26):22875-22885
Trafficking of the proteins that form gap junctions (connexins) from the site of synthesis to the junctional domain appears to require cytoskeletal delivery mechanisms. Although many cell types exhibit specific delivery of connexins to polarized cell sites, such as connexin32 (Cx32) gap junctions specifically localized to basolateral membrane domains of hepatocytes, the precise roles of actin- and tubulin-based systems remain unclear. We have observed fluorescently tagged Cx32 trafficking linearly at speeds averaging 0.25 μm/s in a polarized hepatocyte cell line (WIF-B9), which is abolished by 50 μM of the microtubule-disrupting agent nocodazole. To explore the involvement of cytoskeletal components in the delivery of connexins, we have used a preparation of isolated Cx32-containing vesicles from rat hepatocytes and assayed their ATP-driven motility along stabilized rhodamine-labeled microtubules in vitro. These assays revealed the presence of Cx32 and kinesin motor proteins in the same vesicles. The addition of 50 μM ATP stimulated vesicle motility along linear microtubule tracks with velocities of 0.4-0.5 μm/s, which was inhibited with 1 mM of the kinesin inhibitor AMP-PNP (adenylyl-imidodiphosphate) and by anti-kinesin antibody but only minimally affected by 5 μM vanadate, a dynein inhibitor, or by anti-dynein antibody. These studies provide evidence that Cx32 can be transported intracellularly along microtubules and presumably to junctional domains in cells and highlight an important role of kinesin motor proteins in microtubule-dependent motility of Cx32. 相似文献
99.
Pannexin 1 forms ion and metabolite permeable hexameric channels with abundant expression in the central nervous system and elsewhere. Although pannexin 1 does not form intercellular channels, a common channel topology and oligomerization state, as well as involvement of the intracellular carboxyl terminal (CT) domain in channel gating, is shared with connexins. In this study, we characterized the secondary structure of the mouse pannexin 1 cytoplasmic domains to complement structural studies of the transmembrane segments and compare with similar domains from connexins. A combination of structural prediction tools and circular dichroism revealed that, unlike connexins (predominately intrinsically disordered), cytosolic regions of pannexin 1 contain approximately 50% secondary structure, a majority being α-helical. Moreover, prediction of transmembrane domains uncovered a potential membrane interacting region (I360-G370) located upstream of the caspase cleavage site (D375-D378) within the pannexin 1 CT domain. The α-helical content of a peptide containing these domains (G357-S384) increased in the presence of detergent micelles providing evidence of membrane association. We also purified a pannexin 1 CT construct containing the caspase cleavage site (M374-C426), assigned the resonances by NMR, and confirmed cleavage by Caspase-3 in vitro. On the basis of these structural studies of the cytoplasmic domains of pannexin 1, we propose a mechanism for the opening of pannexin 1 channels upon apoptosis, involving structural changes within the CT domain. 相似文献
100.
Philippa CR Strong Stewart J Hinchliffe Hannah Patrick Steve Atkinson Olivia L Champion Brendan W Wren 《BMC microbiology》2011,11(1):85