全文获取类型
收费全文 | 1380篇 |
免费 | 25篇 |
国内免费 | 29篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 9篇 |
2018年 | 11篇 |
2017年 | 16篇 |
2016年 | 27篇 |
2015年 | 22篇 |
2014年 | 74篇 |
2013年 | 153篇 |
2012年 | 205篇 |
2011年 | 258篇 |
2010年 | 235篇 |
2009年 | 43篇 |
2008年 | 40篇 |
2007年 | 56篇 |
2006年 | 36篇 |
2005年 | 26篇 |
2004年 | 28篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2001年 | 5篇 |
2000年 | 15篇 |
1999年 | 10篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有1434条查询结果,搜索用时 31 毫秒
111.
Rothbard JB Kurnellas MP Brownell S Adams CM Su L Axtell RC Chen R Fathman CG Robinson WH Steinman L 《The Journal of biological chemistry》2012,287(13):9708-9721
The therapeutic benefit of the small heat shock protein αB-crystallin (HspB5) in animal models of multiple sclerosis and ischemia is proposed to arise from its increased capacity to bind proinflammatory proteins at the elevated temperatures within inflammatory foci. By mass spectral analysis, a common set of ~70 ligands was precipitated by HspB5 from plasma from patients with multiple sclerosis, rheumatoid arthritis, and amyloidosis and mice with experimental allergic encephalomyelitis. These proteins were distinguished from other precipitated molecules because they were enriched in the precipitate as compared with their plasma concentrations, and they exhibited temperature-dependent binding. More than half of these ligands were acute phase proteins or members of the complement or coagulation cascades. Consistent with this proposal, plasma levels of HspB5 were increased in patients with multiple sclerosis as compared with normal individuals. The combination of the thermal sensitivity of the HspB5 combined with the high local concentration of these ligands at the site of inflammation is proposed to explain the paradox of how a protein believed to exhibit nonspecific binding can bind with some relative apparent selectivity to proinflammatory proteins and thereby modulate inflammation. 相似文献
112.
113.
114.
SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNA(Sec)) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNA(Sec) to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5'-O-(γ-thio)triphosphate (GTPγS) and guanosine 5'-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (-621, -467, -235, and -275 cal × mol(-1) × K(-1), with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15-19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form. 相似文献
115.
Hiroya Miyamoto Eri Katsuyama Yoshiteru Miyauchi Hiroko Hoshi Kana Miyamoto Yuiko Sato Tami Kobayashi Ryotaro Iwasaki Shigeyuki Yoshida Tomoaki Mori Hiroya Kanagawa Atsuhiro Fujie Wu Hao Hideo Morioka Morio Matsumoto Yoshiaki Toyama Takeshi Miyamoto 《The Journal of biological chemistry》2012,287(39):32479-32484
116.
117.
118.
Sela D Chen L Martin-Brown S Washburn MP Florens L Conaway JW Conaway RC 《The Journal of biological chemistry》2012,287(27):23035-23045
119.
Zoi Diamantopoulou Paraskevi Kitsou Suzanne Menashi Jose Courty Panagiotis Katsoris 《The Journal of biological chemistry》2012,287(48):40339-40349
Pleiotrophin is a growth factor that induces carcinogenesis. Despite the fact that many published reports focused on the role of pleiotrophin and its receptors, receptor protein tyrosine phosphatase (RPTPβ/ζ), and syndecan-3 during tumor development, no information is available regarding their function in tumor metastasis. To investigate the mechanism through which pleiotrophin regulates tumor metastasis, we used two different prostate carcinoma cell lines, DU145 and PC3, in which the expression of RPTPβ/ζ or syndecan-3 was down-regulated by the RNAi technology. The loss of RPTPβ/ζ expression initiated epithelial-to-mesenchymal transition (EMT) and increased the ability of the cells to migrate and invade. Importantly, the loss of RPTPβ/ζ expression increased metastasis in nude mice in an experimental metastasis assay. We also demonstrate that RPTPβ/ζ counterbalanced the pleiotrophin-mediated syndecan-3 pathway. While the inhibition of syndecan-3 expression inhibited the pleiotrophin-mediated cell migration and attachment through the Src and Fak pathway, the inhibition of RPTPβ/ζ expression increased pleiotrophin-mediated migration and attachment through an interaction with Src and the subsequent activation of a signal transduction pathway involving Fak, Pten, and Erk1/2. Taken together, these results suggest that the loss of RPTPβ/ζ may contribute to the metastasis of prostate cancer cells by inducing EMT and promoting pleiotrophin activity through the syndecan-3 pathway. 相似文献