全文获取类型
收费全文 | 3725篇 |
免费 | 252篇 |
国内免费 | 3篇 |
出版年
2022年 | 11篇 |
2021年 | 38篇 |
2020年 | 25篇 |
2019年 | 33篇 |
2018年 | 56篇 |
2017年 | 51篇 |
2016年 | 79篇 |
2015年 | 137篇 |
2014年 | 155篇 |
2013年 | 310篇 |
2012年 | 237篇 |
2011年 | 243篇 |
2010年 | 169篇 |
2009年 | 136篇 |
2008年 | 232篇 |
2007年 | 227篇 |
2006年 | 215篇 |
2005年 | 243篇 |
2004年 | 235篇 |
2003年 | 219篇 |
2002年 | 208篇 |
2001年 | 55篇 |
2000年 | 55篇 |
1999年 | 57篇 |
1998年 | 50篇 |
1997年 | 31篇 |
1996年 | 39篇 |
1995年 | 22篇 |
1994年 | 24篇 |
1993年 | 28篇 |
1992年 | 29篇 |
1991年 | 24篇 |
1990年 | 26篇 |
1989年 | 22篇 |
1988年 | 28篇 |
1987年 | 19篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 21篇 |
1983年 | 12篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 17篇 |
1979年 | 14篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 9篇 |
1974年 | 6篇 |
1973年 | 10篇 |
1971年 | 5篇 |
排序方式: 共有3980条查询结果,搜索用时 31 毫秒
1.
2.
U6 small nuclear RNA (U6 snRNA) is one of the spliceosomal RNAs essential for pre-mRNA splicing. Highly conserved region of U6 snRNA shows a structural similarity with the catalytic center of the negative strand of the satellite RNA of tobacco ring spot virus [(-)sTRSV], supporting the hypothesis that U6 snRNA has a catalytic role in pre-mRNA splicing. To test this hypothesis, we examined in vitro whether synthetic RNAs consisting of the sequence of the highly conserved region of U6 snRNA or various chimeric RNAs between the U6 region and the catalytic center of (-)sTRSV could cleave a substrate RNA that can partially base-pair with them and has a GU sequence between the pairing regions. Chimeric RNAs with 70 to 83% sequence identity with the conserved region of S. pombe U6 snRNA cleaved the substrate RNA at the 5' side of the GU sequence. In addition, we found that the highly conserved region of U6 snRNA is similar in structure to the catalytic core region of the group I self-splicing intron in cyanobacteria. These results support the hypothesis that U6 snRNA catalyzes the pre-mRNA splicing reaction and U6 snRNA may originate from the catalytic domain of an ancient self-splicing intron. 相似文献
3.
Y Tani I Ohkubo S Higashiyama M Kunimatsu M Sasaki 《Comparative biochemistry and physiology. B, Comparative biochemistry》1987,88(2):429-441
1. High mol. wt kininogen (HMW kininogen) was purified to a homogeneous state from porcine plasma. 2. The protein exhibited a strong inhibitory activity for thiol proteinases such as ficin, papain and calpain I, whereas it did not inhibit serine proteinases, trypsin and chymotrypsin. 3. The mol. wt, isoelectric point, amino acid and carbohydrate compositions, stabilities to temperature and pH, kinetic constants, and immunological properties of the porcine HMW kininogen were determined and compared with those of human HMW kininogen. 相似文献
4.
In several vascular inflammatory reactions (i.e. immunity and thrombosis) inflammatory mediators lead to the activation of vascular endothelial cells (EC). To date, a number
of functional molecules induced on the surface of activated-EC have been identified. We report here that Globotetraosylceramide
(Gb4), a glycosphingolipid expressed in EC, is a novel inducible molecule on EC activated by TNF-α. The cell surface expression
of Gb4 is increased in a time-dependent manner under TNF-α stimulation, which shows distinct expression kinetics of major
proteins induced by TNF-α on EC. MALDI-TOF-MS analysis revealed that the enhanced Gb4 predominantly contains C24:0 fatty acid
in the ceramide moiety. Isolated caveolae/lipid raft-enriched detergent insoluble membrane domains in activated-EC predominantly
contain this molecular species of Gb4. Gb4 containing C16:0 fatty acid in the ceramide moiety, which is known to constitute
the major species of Gb4 in plasma, is also found as a major molecular species in EC. These observations indicate that Gb4,
especially with very long fatty acid, is enhanced in EC during its inflammatory reaction, and suggest the potential utility
of Gb4 as a biomarker for monitoring inflammation status of EC involving its related diseases. 相似文献
5.
Tetsuya Kawai Iwase Kazuhiko Noriko Takaya Yuko Yamaguchi Ryuta Kishii Yasushi Kohno Haruaki Kurasaki 《Bioorganic & medicinal chemistry letters》2017,27(4):1045-1049
We attempted to optimize sulfonamide-based non-alkyne LpxC inhibitors by focusing on improvements in enzyme inhibitory and antibacterial activity. It was discovered that inhibitors possessing 2-aryl benzofuran as a hydrophobe exhibited good activity. In particular, compound 21 displayed impressive antibacterial activity (E. coli MIC = 0.063 μg/mL, K. pneumoniae MIC = 0.5 μg/mL, and P. aeruginosa MIC = 0.5 μg/mL), and is a promising lead for further exploration as an antibacterial agent. 相似文献
6.
M Muraguchi Y Yoshihara T Tunemitu I Tani T Higuti 《Biochemical and biophysical research communications》1990,168(1):226-231
Previous studies suggested that the hydrophobic protein chargerin II, which is encoded in the A6L of mitochondrial DNA, may have a key role in the energy transduction by mitochondrial H(+)-ATP synthase because an antibody against chargerin II inhibited ATP synthesis and ATP-Pi exchange, in an energy-dependent fashion. In the present work, the contents of chargerin II in the H(+)-ATP synthase purified from rat liver mitochondria and in submitochondrial particles were determined by radioimmunoassay. Results showed that the H(+)-ATP synthase contained chargerin II in a molar ratio of one to one. This is the first report on the stoichiometry of the A6L-product in mitochondrial H(+)-ATP synthase. 相似文献
7.
Tetsuya Akamatsu 《Developmental biology》2009,325(2):434-443
The submandibular gland (SMG) develops through the epithelial-mesenchymal interaction mediated by many growth/differentiation factors including activin and BMPs, which are synthesized as inactive precursors and activated by subtilisin-like proprotein convertases (SPC) following cleavage at their R-X-K/R-R site. Here, we found that Dec-RVKR-CMK, a potent inhibitor of SPC, inhibited the branching morphogenesis of the rat embryonic SMG, and caused low expression of a water channel AQP5, in an organ culture system. Dec-RVKR-CMK also decreased the expression of PACE4, a SPC member, but not furin, another SPC member, suggesting the involvement of PACE4 in the SMG development. Heparin, which is known to translocate PACE4 in the extracellular matrix into the medium, and an antibody specific for the catalytic domain of PACE4, both reduced the branching morphogenesis and AQP5 expression in the SMG. The inhibitory effects of Dec-RVKR-CMK were partially rescued by the addition of recombinant BMP2, whose precursor is one of the candidate substrates for PACE4 in vivo. Further, the suppression of PACE4 expression by siRNAs resulted in decreased expression of AQP5 and inhibition of the branching morphogenesis in the present organ culture system. These observations suggest that PACE4 regulates the SMG development via the activation of some growth/differentiation factors. 相似文献
8.
Sakayu Shimizu Keiko Inoue Yoshiki Tani Hideaki Yamada 《Biochemical and biophysical research communications》1981,103(4):1231-1237
The preparation of highly purified medium chain acyl-CoA synthetase (Acid: CoA ligase, AMP-forming (EC 6.2.1.2)) from the cell extracts of is described. The enzyme is inducibly formed in the cells of the microorganism, when it is grown with butyrate as a major carbon source. The purified enzyme is homogeneous on disc gel electrophoresis. Its molecular weight is approximately 142,000, and it is possibly composed of 4 identical subunits of approximately 37,000 molecular weight and has isoelectric point of 4.3. The enzyme catalyzes the stoichiometric conversion of butyrate and CoA to butyryl-CoA in the presence of ATP and Mg2+. It also activates fatty acids with carbon chain lengths of 3 to 5 well, but is inactive toward fatty acids with carbon chain lengths of more than 6. The enzyme is sulfhydryl dependent and inactivated by silver and mercury compounds. 相似文献
9.
H Okazaki C Tani M Ando K Ishii S Ishibashi Y Nishimura K Kato 《Journal of biochemistry》1992,112(3):409-413
A previously found proteinase possibly involved in the modification of hexokinase to eliminate the mitochondria-binding ability without appreciable change in the catalytic activity (called hexokinase-processing enzyme hereafter), was purified by sequential chromatographies from rat liver and its properties were examined. The hexokinase-processing enzyme had carbohydrate moieties as evidenced by adsorption on immobilized concanavalin A, and had a molecular weight of about 23,000 as estimated by SDS-PAGE and gel filtration chromatography. Benzyloxycarbonyl-phenylalanyl-L-arginine-4-methylcoumaryl-7-amide (Z-Phe-Arg-MCA)-hydrolyzing activity was co-purified with this processing activity throughout the purification, while the hydrolyzing activity for benzyloxycarbonyl-L-arginyl-L-arginine-4-methylcoumaryl-7-amide (Z-Arg-Arg-MCA) was not. The processing activity, as well as Z-Phe-Arg-MCA hydrolyzing activity, was highly sensitive to cysteine proteinase inhibition, for example, by leupeptin and N-[N-3-(trans-carboxirane-2-carbonyl)-L-leucyl]agmatine (E-64). Furthermore, the enzyme preparation reacted with an antibody against cathepsin L purified from rat kidney. These results indicated that cathepsin L may be involved in the above-mentioned processing of hexokinase. 相似文献