全文获取类型
收费全文 | 2147篇 |
免费 | 125篇 |
专业分类
2272篇 |
出版年
2023年 | 9篇 |
2022年 | 16篇 |
2021年 | 54篇 |
2020年 | 29篇 |
2019年 | 40篇 |
2018年 | 47篇 |
2017年 | 46篇 |
2016年 | 69篇 |
2015年 | 91篇 |
2014年 | 114篇 |
2013年 | 130篇 |
2012年 | 187篇 |
2011年 | 166篇 |
2010年 | 114篇 |
2009年 | 101篇 |
2008年 | 162篇 |
2007年 | 128篇 |
2006年 | 120篇 |
2005年 | 133篇 |
2004年 | 121篇 |
2003年 | 101篇 |
2002年 | 86篇 |
2001年 | 16篇 |
2000年 | 16篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 14篇 |
1996年 | 8篇 |
1995年 | 13篇 |
1994年 | 6篇 |
1993年 | 12篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 1篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1974年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有2272条查询结果,搜索用时 15 毫秒
151.
Masakatsu Kamiya Keisuke Oyauchi Yoshinori Sato Takuya Yokoyama Mofei Wang Tomoyasu Aizawa Yasuhiro Kumaki Mineyuki Mizuguchi Kunio Imai Makoto Demura Koichi Suzuki Keiichi Kawano 《Journal of peptide science》2010,16(5):242-248
We previously reported that yamamarin, a pentapeptide with an amidated C‐terminus (DILRG‐NH2) isolated from larvae of the silkmoth, and its palmitoylated analog (C16‐DILRG‐NH2) suppressed proliferation of rat hepatoma (liver cancer) cells. In this study, we investigated the structure–activity relationship of yamamarin by in vitro assay and spectroscopic methods (CD and NMR) for various analogs. The in vitro assay results demonstrated that the chemical structure of the C‐terminal part (‐RG‐NH2) of yamamarin is essential for its activity. The CD and NMR results indicated that yamamarin and its analog adopt predominantly a random coil conformation. Moreover, a comparison of NMR spectra of DILRG‐NH2 and C16‐DILRG‐NH2 revealed that the N‐terminal palmitoyl group of C16‐DILRG‐NH2 did not affect the conformation of the C‐terminal part, which is essential for activity. Together, these results should assist in the design of more sophisticated anticancer drugs. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
152.
153.
Osami Shoji Takashi Fujishiro Shingo Nagano Shota Tanaka Takuya Hirose Yoshitsugu Shiro Yoshihito Watanabe 《Journal of biological inorganic chemistry》2010,15(8):1331-1339
Cytochrome P450BSβ, a H2O2-dependent cytochrome P450 catalyzing the hydroxylation of long-alkyl-chain fatty acids, lacks the general acid–base residue
around the heme, which is indispensable for the efficient generation of the active species using H2O2. On the basis of the crystal structure of the palmitic acid bound form of cytochrome P450BSβ, it was suggested that the role of the general acid–base function was provided by the carboxylate group of fatty acids. The
participation of the carboxylate group of the substrate was supported by the fact that cytochrome P450BSβ can catalyze oxidations of nonnatural substrates such as styrene and ethylbenzene in the presence of a series of short-alkyl-chain
carboxylic acids as a dummy molecule of fatty acid. We refer to a series of short-alkyl-chain carboxylic acids as a “decoy
molecule”. As shown here, we have clarified the crystal structure of the decoy-molecule-bound form and elucidated that the
location of its carboxylate group is virtually the same as that of palmitic acid in the heme cavity, indicating that the carboxylate
group of the decoy molecule serves as the general acid–base catalyst. This result further confirms that the role of the acid–base
function is satisfied by the carboxylate group of the substrates. In addition, the structure analysis of the substrate-free
form has clarified that no remarkable structural change is induced by the binding of the decoy molecule as well as fatty acid.
Consequently, whether the carboxylate group is positioned in the active site provides the switching mechanism of the catalytic
cycle of cytochrome P450BSβ. 相似文献
154.
Takuma Suematsu Shin‐ichi Yokobori Hiroyuki Morita Shigeo Yoshinari Takuya Ueda Kiyoshi Kita Nono Takeuchi Yoh‐ichi Watanabe 《Molecular microbiology》2010,75(6):1445-1454
Translation elongation factor G (EF‐G) in bacteria plays two distinct roles in different phases of the translation system. EF‐G catalyses the translocation of tRNAs on the ribosome in the elongation step, as well as the dissociation of the post‐termination state ribosome into two subunits in the recycling step. In contrast to this conventional view, it has very recently been demonstrated that the dual functions of bacterial EF‐G are distributed over two different EF‐G paralogues in human mitochondria. In the present study, we show that the same division of roles of EF‐G is also found in bacteria. Two EF‐G paralogues are found in the spirochaete Borrelia burgdorferi, EF‐G1 and EF‐G2. We demonstrate that EF‐G1 is a translocase, while EF‐G2 is an exclusive recycling factor. We further demonstrate that B. burgdorferi EF‐G2 does not require GTP hydrolysis for ribosome disassembly, provided that translation initiation factor 3 (IF‐3) is present in the reaction. These results indicate that two B. burgdorferi EF‐G paralogues are close relatives to mitochondrial EF‐G paralogues rather than the conventional bacterial EF‐G, in both their phylogenetic and biochemical features. 相似文献
155.
156.
Manabu Yamada Mitsuji Yamashita Takuya Suyama Junko Yamashita Kazuhide Asai Taishi Niimi Nobuhisa Ozaki Michio Fujie Kasthuraiah Maddali Satoki Nakamura Kazunori Ohnishi 《Bioorganic & medicinal chemistry letters》2010,20(19):5943-5946
4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect. 相似文献
157.
Kazuyoshi Ohkawa Tetsuo Takehara Hisashi Ishida Masanori Kagita Takuya Miyagi Norio Hayashi 《Biochemical and biophysical research communications》2010,394(3):574-580
Factors involved in transition from the immunotolerant to immunoactive phase in chronic hepatitis B virus (HBV) infection remain unclear. We investigated viral mutations occurring during transition and elucidated their virological and immunological significance. Full-length HBV DNA sequences were serially determined in a chronic HBV carrier from the immunotolerant to immunoactive phase. Viral replicative competence was examined by transfection analysis. HBV-specific CD8+ T cell response was evaluated by coculture of CD8+ T cells with autologous dendritic cells followed by interferon-γ Elispot assay. Eleven point mutations and two deletions appeared around the onset of the immunoactive phase. Viral replicative competence declined significantly after the onset of active hepatitis. Examination of the CD8+ T cell response against two putative T-cell epitopes, which contained substituted amino acids from the immunotolerant to immunoactive phase, showed that mutant HBV epitopes gave a lesser T cell response than wild-type HBV ones. In summary, point mutations and deletions may occur prior to or concurrent with the onset of the immunoactive phase during chronic HBV infection. These mutations may result in a significant decrease in both viral replicative competence and HBV-specific CD8+ T cell response, suggesting a possible adaptation for the maintenance of viral persistence. 相似文献
158.
Understanding the role of geography and ecology in species divergence is central to the study of evolutionary diversification. We used climatic, geographic, and biological data from nine wild Andean tomato species to describe each species' ecological niche and to evaluate the likely ecological and geographical modes of speciation in this clade. Using data from >1000 wild accessions and publicly available data derived from geographic information systems for various environmental variables, we found most species pairs were significantly differentiated for one or more environmental variables. By comparing species' predicted niches generated by species distribution modeling (SDM), we found significant niche differentiation among three of four sister-species pairs, suggesting ecological divergence is consistently associated with recent divergence. In comparison, based on age-range correlation (ARC) analysis, there was no evidence for a predominant geographical (allopatric vs. sympatric) context for speciation in this group. Overall, our results suggest an important role for environmentally mediated differentiation, rather than simply geographical isolation, in species divergence. 相似文献
159.
160.