全文获取类型
收费全文 | 1398篇 |
免费 | 97篇 |
出版年
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 13篇 |
2019年 | 7篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 19篇 |
2015年 | 27篇 |
2014年 | 49篇 |
2013年 | 48篇 |
2012年 | 66篇 |
2011年 | 83篇 |
2010年 | 38篇 |
2009年 | 47篇 |
2008年 | 78篇 |
2007年 | 84篇 |
2006年 | 88篇 |
2005年 | 77篇 |
2004年 | 84篇 |
2003年 | 64篇 |
2002年 | 71篇 |
2001年 | 48篇 |
2000年 | 41篇 |
1999年 | 51篇 |
1998年 | 20篇 |
1997年 | 22篇 |
1996年 | 20篇 |
1995年 | 23篇 |
1994年 | 21篇 |
1993年 | 8篇 |
1992年 | 27篇 |
1991年 | 26篇 |
1990年 | 11篇 |
1989年 | 19篇 |
1988年 | 14篇 |
1987年 | 15篇 |
1986年 | 12篇 |
1985年 | 22篇 |
1984年 | 15篇 |
1983年 | 11篇 |
1981年 | 6篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1941年 | 4篇 |
1933年 | 4篇 |
排序方式: 共有1495条查询结果,搜索用时 15 毫秒
81.
Ui A Satoh Y Onoda F Miyajima A Seki M Enomoto T 《Molecular genetics and genomics : MGG》2001,265(5):837-850
The SGS1 gene of Saccharomyces (cerevisiae is a homologue of the genes affected in Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome. Disruption of the SGS1 gene is associated with high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea (HU), and with hyper-recombination phenotypes, including interchromosomal recombination between heteroalleles. SGS1 encodes a protein which has a helicase domain similar to that of Escherichia coli RecQ. A comparison of amino acid sequences among helicases of the RecQ family reveals that Sgs1,WRN, and BLM share a conserved region adjacent to the C-terminal part of the helicase domain (C-terminal conserved region). In addition, Sgs1 contains two highly charged acidic regions in its N-terminal region and the HRDC (helicase and RNaseD C-terminal) domain at its C-terminal end. These regions were also found in BLM and WRN, and in Rqh1 from Schizosaccharomyces pombe. In this study, we demonstrate that the C-terminal conserved region, as well as the helicase motifs, of Sgs1 are essential for complementation of MMS sensitivity and suppression of hyper-recombination in sgs1 mutants. In contrast, the highly charged acidic regions, the HRDC domain, and the C-terminal 252 amino acids were dispensable for the complementation of these phenotypes. Surprisingly, the N-terminal 45 amino acids of Sgs1 were absolutely required for the suppression of the above phenotypes. Introduction of missense mutations into the region encoding amino acids 4-13 abolished the ability of Sgsl to complement MMS sensitivity and suppress hyper-recombination in sgs1 mutants, and also prevented its interaction with Top3, indicating that interaction with Top3 via the N-terminal region of Sgs1 is involved in the complementation of MMS sensitivity and the suppression of hyper-recombination. 相似文献
82.
Takao M Kanno S Shiromoto T Hasegawa R Ide H Ikeda S Sarker AH Seki S Xing JZ Le XC Weinfeld M Kobayashi K Miyazaki J Muijtjens M Hoeijmakers JH van der Horst G Yasui A Sarker AH 《The EMBO journal》2002,21(13):3486-3493
Endonuclease III, encoded by nth in Escherichia coli, removes thymine glycols (Tg), a toxic oxidative DNA lesion. To determine the biological significance of this repair in mammals, we established a mouse model with mutated mNth1, a homolog of nth, by gene targeting. The homozygous mNth1 mutant mice showed no detectable phenotypical abnormality. Embryonic cells with or without wild-type mNth1 showed no difference in sensitivity to menadione or hydrogen peroxide. Tg produced in the mutant mouse liver DNA by X-ray irradiation disappeared with time, though more slowly than in the wild-type mouse. In extracts from mutant mouse liver, we found, instead of mNTH1 activity, at least two novel DNA glycosylase activities against Tg. One activity is significantly higher in the mutant than in wild-type mouse in mitochondria, while the other is another nuclear glycosylase for Tg. These results underscore the importance of base excision repair of Tg both in the nuclei and mitochondria in mammals. 相似文献
83.
Sakuraba H Yoshioka I Koga S Takahashi M Kitahama Y Satomura T Kawakami R Ohshima T 《The Journal of biological chemistry》2002,277(15):12495-12498
A gene encoding an ADP-dependent phosphofructokinase homologue has been identified in the hyperthermophilic archaeon Methanococcus jannaschii via genome sequencing. The gene encoded a protein of 462 amino acids with a molecular weight of 53,361. The deduced amino acid sequence of the gene showed 52 and 29% identities to the ADP-dependent phosphofructokinase and glucokinase from Pyrococcus furiosus, respectively. The gene was overexpressed in Escherichia coli, and the produced enzyme was purified and characterized. To our surprise, the enzyme showed high ADP-dependent activities for both glucokinase and phosphofructokinase. A native molecular mass was estimated to be 55 kDa, and this indicates the enzyme is monomeric. The reaction rate for the phosphorylation of D-glucose was almost 3 times that for D-fructose 6-phosphate. The K(m) values for D-fructose 6-phosphate and D-glucose were calculated to be 0.010 and 1.6 mm, respectively. The K(m) values for ADP were 0.032 and 0.63 mm when D-glucose and D-fructose 6-phosphate were used as a phosphoryl group acceptor, respectively. The gene encoding the enzyme is proposed to be an ancestral gene of an ADP-dependent phosphofructokinase and glucokinase. A gene duplication event might lead to the two enzymatic activities. 相似文献
84.
Chabot S Kashio Y Seki M Shirato Y Nakamura K Nishi N Nakamura T Matsumoto R Hirashima M 《Glycobiology》2002,12(2):111-118
Ecalectin/galectin-9 was recently described as a novel eosinophil chemoattractant highly expressed in immune tissues. We investigated the regulation of galectin-9 expression and release in Jurkat (a T cell line) cells. We demonstrated that medium and long-sized galectin-9 isoforms were constitutively expressed, and phorbol 12-myriastate 13-acetate (PMA) upregulated the level of galectin-9 mRNA in Jurkat cells. Western blotting and flow cytometry analyses revealed that PMA stimulation resulted in the upregulation of both intracellular and surface galectin-9 protein. The stimulated Jurkat cells simultaneously released evident eosinophil chemoattractant activity (ECA). Main ECA was adsorbed by both lactose and anti-galectin-9 antibody affinity column, suggesting that the ECA was ascribed to galectin-9. When Jurkat cells were stimulated with PMA in the presence of a BB94, a matrix metalloproteinase (MMP) inhibitor, but not tissue inhibitor of metalloproteinase-1 (TIMP-1), the release of galectin-9 was suppressed in a dose-dependent manner. We further found that calphostin c, a protein kinase c (PKC) inhibitor, weakly but significantly suppressed the release of galectin-9. The present data suggested that galectin-9 production in Jurkat cells is provoked by the stimulation with PMA and that some MMP and PKC is, at least, partly involved in the release of galectin-9 from Jurkat cells. 相似文献
85.
In the last two decades, multiple aspects of the peptide YY (PYY) secretion have been investigated. Besides fat and fatty acids, many luminal nutrients in the distal intestine appear to induce PYY release. Some studies have shown that bile acid, but not nutrients, plays a crucial role in the regulation of PYY secretion. Moreover, chyme in the proximal intestine also regulates the peptide release by indirect action through humoral and neuronal factors. Gastrin, cholecystokinin, and the vagus nerve are major candidates for mediators of these indirect actions. Several growth factors have been shown to regulate PYY synthesis in mucosa of the distal intestine. This review is aimed at presenting an overview of these recent studies on PYY secretion in the distal intestine. 相似文献
86.
Yanagita M Shimabukuro Y Nozaki T Yoshimura N Watanabe J Koide H Terakura M Saho T Takedachi M Jang MH Kiyono H Murakami S 《Biochemical and biophysical research communications》2002,297(2):329-334
To investigate the biological activity of epithelial cells in view of host defense, we analyzed the mRNA expression of inducible NOS (iNOS) as well as NO production by human gingival epithelial cells (HGEC) stimulated with IL-15. RT-PCR analysis revealed that HGEC expressed IL-15 receptor alpha-chain mRNA. In addition, stimulation with IL-15 enhanced iNOS expression by HGEC through an increase of both mRNA and protein levels. Moreover, IL-15 up-regulated the production of NO(2)(-)/NO(3)(-), a NO-derived stable end product, from HGEC. The enhanced NO production by IL-15 was inhibited by AMT, an iNOS-specific inhibitor. These results suggest that IL-15 is a potent regulator of iNOS expression by HGEC and involved in innate immunity in the mucosal epithelium. 相似文献
87.
88.
89.
Narusaka Y Narusaka M Seki M Ishida J Nakashima M Kamiya A Enju A Sakurai T Satoh M Kobayashi M Tosa Y Park P Shinozaki K 《Plant & cell physiology》2003,44(4):377-387
The hypersensitive response (HR) was induced in a wild-type Arabidopsis thaliana plant (Columbia) (Col-wt) by inoculation with Alternaria brassicicola that causes the development of small brown necrotic lesions on the leaves. By contrast, pad3-1 mutants challenged with A. brassicicola produced spreading lesions. The cell death in pad3-1 mutants could not inhibit the pathogen growth and development, although both production of H(2)O(2) and localized cell death were similar in Col-wt and pad3-1 plants after the inoculation. The difference between Col-wt and pad3-1 plants is defense responses after the occurrence of cell death. In other words, PAD3 is necessary for defense response to A. brassicicola. Therefore, we examined the changes in the expression patterns of ca. 7,000 genes by cDNA microarray analysis after inoculation with A. brassicicola. The cDNA microarrays were also done to analyze Arabidopsis responses after treatment with signal molecules, reactive oxygen species (ROS)-inducing compounds and UV-C. The results suggested that the pad3-1 mutation altered not only the accumulation of camalexin but also the timing of expression of many defense-related genes in response to the challenge with A. brassicicola. Furthermore, the plants integrate two or more signals that act together for promoting the induction of multiple defense pathways. 相似文献
90.