全文获取类型
收费全文 | 2412篇 |
免费 | 121篇 |
专业分类
2533篇 |
出版年
2023年 | 11篇 |
2022年 | 16篇 |
2021年 | 55篇 |
2020年 | 29篇 |
2019年 | 45篇 |
2018年 | 52篇 |
2017年 | 48篇 |
2016年 | 78篇 |
2015年 | 98篇 |
2014年 | 118篇 |
2013年 | 137篇 |
2012年 | 203篇 |
2011年 | 190篇 |
2010年 | 121篇 |
2009年 | 112篇 |
2008年 | 172篇 |
2007年 | 122篇 |
2006年 | 124篇 |
2005年 | 131篇 |
2004年 | 128篇 |
2003年 | 107篇 |
2002年 | 99篇 |
2001年 | 19篇 |
2000年 | 24篇 |
1999年 | 49篇 |
1998年 | 18篇 |
1997年 | 18篇 |
1996年 | 11篇 |
1995年 | 13篇 |
1994年 | 9篇 |
1993年 | 14篇 |
1992年 | 17篇 |
1991年 | 16篇 |
1990年 | 20篇 |
1989年 | 18篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1968年 | 4篇 |
1967年 | 4篇 |
1966年 | 5篇 |
排序方式: 共有2533条查询结果,搜索用时 15 毫秒
961.
Takuya Mori Norikazu Maeda Kana Inoue Ryohei Sekimoto Yu Tsushima Keisuke Matsuda Masaya Yamaoka Takayoshi Suganami Hitoshi Nishizawa Yoshihiro Ogawa Tohru Funahashi Iichiro Shimomura 《PloS one》2013,8(10)
Aims
Ephrin-B1 (EfnB1) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity.Methods and Results
EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression.Conclusions
EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation. 相似文献962.
963.
964.
Takuya Sugahara Keiko Ueno-Shuto Eriko Watanabe Kenichiro Kitamura Ai Mizuno Mary Ann Suico 《Experimental cell research》2009,315(19):3294-24
Epithelial sodium channel (ENaC) is a heteromultimeric Na+ channel at the apical membrane in the kidney, colon, and lung. Because ENaC plays a crucial role in regulating Na+ absorption and extracellular fluid volume, its dysregulation causes severe phenotypes including hypertension, hypokalemia, and airway obstruction. Despite the importance of ENaC, its protein quality control mechanism remains less established. Here we firstly show the role of calreticulin (CRT), a lectin-like molecular chaperone in the endoplasmic reticulum (ER), on the regulation of ENaC. Overexpression and knockdown analyses clearly indicated that CRT positively affects the expression of each ENaC subunit (α, β and γ). CRT overexpression also up-regulated the cell surface expression of α-, β- and γ-ENaC. Moreover, we found that CRT directly interacts with each ENaC subunit. Although CRT knockdown did not affect the de novo synthesis of ENaC subunits, CRT overexpression decreased α-, β- and γ-ENaC expression in the detergent (RIPA)-insoluble fraction, suggesting that CRT enhanced the solubility of ENaC subunits. Consistent with the increased intracellular and cell surface expression of ENaC subunits, increased channel activity of ENaC was also observed upon overexpression of CRT. Our study thus identifies CRT as an ER chaperone that regulates ENaC expression and function. 相似文献
965.
966.
Takuya Miyake Jun Nakajima Keitaro Umemura Norio Onikura Takayoshi Ueda Carl Smith Kouichi Kawamura 《Journal of fish biology》2021,99(5):1677-1695
The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn-spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life-history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55–0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (<0.10 Ma) was suggested in many of the lineages, which accords with other freshwater fishes. Biogeographically the ancestral A. rhombeus/A. barbatulus was likely to have repeatedly colonized Japan from the continent through land bridges in the late Pliocene and the early Pleistocene. However, the close genetic relationship between Japanese A. rhombeus and A. barbatulus suggests another possibility, with the second colonization occurring in reverse, from Japan to China. The small genetic distance between them indicates that the colonization occurred later than colonization events of other freshwater fishes, including other bitterling species. 相似文献
967.
Maruoka M Sato M Yuan Y Ichiba M Fujii R Ogawa T Ishida-Kitagawa N Takeya T Watanabe N 《The Biochemical journal》2012,441(3):889-899
Mena [mammalian Ena (Enabled)]/VASP (vasodilator-stimulated phosphoprotein) proteins are the homologues of Drosophila Ena. In Drosophila, Ena is a substrate of the tyrosine kinase DAbl (Drosophila Abl). However, the link between Abl and the Mena/VASP family is not fully understood in mammals. We previously reported that Abi-1 (Abl interactor 1) promotes phosphorylation of Mena and BCAP (B-cell adaptor for phosphoinositide 3-kinase) by bridging the interaction between c-Abl and the substrate. In the present study we have identified VASP, another member of the Mena/VASP family, as an Abi-1-bridged substrate of Abl. VASP is phosphorylated by Abl when Abi-1 is co-expressed. We also found that VASP interacted with Abi-1 both in vitro and in vivo. VASP was tyrosine-phosphorylated in Bcr-Abl-positive leukaemic cells in an Abi-1-dependent manner. Co-expression of c-Abl and Abi-1 or the phosphomimetic Y39D mutation in VASP resulted in less accumulation of VASP at focal adhesions. VASP Y39D had a reduced affinity to the proline-rich region of zyxin. Interestingly, overexpression of both phosphomimetic and unphosphorylated forms of VASP, but not wild-type VASP, impaired adhesion of K562 cells to fibronectin. These results suggest that the phosphorylation and dephosphorylation cycle of VASP by the Abi-1-bridged mechanism regulates association of VASP with focal adhesions, which may regulate adhesion of Bcr-Abl-transformed leukaemic cells. 相似文献
968.
Watanabe HC Welke K Schneider F Tsunoda S Zhang F Deisseroth K Hegemann P Elstner M 《The Journal of biological chemistry》2012,287(10):7456-7466
Channelrhodopsins (ChRs) are light-gated cation channels that mediate ion transport across membranes in microalgae (vectorial catalysis). ChRs are now widely used for the analysis of neural networks in tissues and living animals with light (optogenetics). For elucidation of functional mechanisms at the atomic level, as well as for further engineering and application, a detailed structure is urgently needed. In the absence of an experimental structure, here we develop a structural ChR model based on several molecular computational approaches, capitalizing on characteristic patterns in amino acid sequences of ChR1, ChR2, Volvox ChRs, Mesostigma ChR, and the recently identified ChR of the halophilic alga Dunaliella salina. In the present model, we identify remarkable structural motifs that may explain fundamental electrophysiological properties of ChR2, ChR1, and their mutants, and in a crucial validation of the model, we successfully reproduce the excitation energy predicted by absorption spectra. 相似文献
969.
970.