全文获取类型
收费全文 | 1714篇 |
免费 | 144篇 |
国内免费 | 1篇 |
专业分类
1859篇 |
出版年
2023年 | 5篇 |
2022年 | 12篇 |
2021年 | 23篇 |
2020年 | 16篇 |
2019年 | 28篇 |
2018年 | 25篇 |
2017年 | 27篇 |
2016年 | 55篇 |
2015年 | 80篇 |
2014年 | 97篇 |
2013年 | 115篇 |
2012年 | 145篇 |
2011年 | 151篇 |
2010年 | 84篇 |
2009年 | 72篇 |
2008年 | 100篇 |
2007年 | 96篇 |
2006年 | 87篇 |
2005年 | 118篇 |
2004年 | 73篇 |
2003年 | 115篇 |
2002年 | 90篇 |
2001年 | 26篇 |
2000年 | 14篇 |
1999年 | 22篇 |
1998年 | 18篇 |
1997年 | 21篇 |
1996年 | 19篇 |
1995年 | 18篇 |
1994年 | 11篇 |
1993年 | 13篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 3篇 |
1989年 | 12篇 |
1988年 | 8篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1966年 | 1篇 |
1958年 | 2篇 |
1939年 | 1篇 |
排序方式: 共有1859条查询结果,搜索用时 15 毫秒
81.
We consider array experiments that compare expression levels of a high number of genes in two cell lines with few repetitions and with no subject effect. We develop a statistical model that illustrates under which assumptions thresholding is optimal in the analysis of such microarray data. The results of our model explain the success of the empirical rule of two-fold change. We illustrate a thresholding procedure that is adaptive to the noise level of the experiment, the amount of genes analyzed, and the amount of genes that truly change expression level. This procedure, in a world of perfect knowledge on noise distribution, would allow reconstruction of a sparse signal, minimizing the false discovery rate. Given the amount of information actually available, the thresholding rule described provides a reasonable estimator for the change in expression of any gene in two compared cell lines. 相似文献
82.
Plastids are the site of the reductive and the oxidative pentose phosphate pathways, which both generate pentose phosphates as intermediates. A plastidic transporter from Arabidopsis has been identified that is able to transport, in exchange with inorganic phosphate or triose phosphates, xylulose 5-phosphate (Xul-5-P) and, to a lesser extent, also ribulose 5-phosphate, but does not accept ribose 5-phosphate or hexose phosphates as substrates. Under physiological conditions, Xul-5-P would be the preferred substrate. Therefore, the translocator was named Xul-5-P/phosphate translocator (XPT). The XPT shares only approximately 35% to 40% sequence identity with members of both the triose phosphate translocator and the phosphoenolpyruvate/phosphate translocator classes, but a higher identity of approximately 50% to glucose 6-phosphate/phosphate translocators. Therefore, it represents a fourth group of plastidic phosphate translocators. Database analysis revealed that plant cells contain, in addition to enzymes of the oxidative branch of the oxidative pentose phosphate pathway, ribose 5-phosphate isomerase and ribulose 5-phosphate epimerase in both the cytosol and the plastids, whereas the transketolase and transaldolase converting the produced pentose phosphates to triose phosphates and hexose phosphates are probably solely confined to plastids. It is assumed that the XPT function is to provide the plastidic pentose phosphate pathways with cytosolic carbon skeletons in the form of Xul-5-P, especially under conditions of a high demand for intermediates of the cycles. 相似文献
83.
84.
Innate and acquired immunity in atherogenesis 总被引:33,自引:0,他引:33
Binder CJ Chang MK Shaw PX Miller YI Hartvigsen K Dewan A Witztum JL 《Nature medicine》2002,8(11):1218-1226
85.
Sulfatide is associated with insulin granules and located to microdomains of a cultured beta cell line 总被引:1,自引:0,他引:1
Blomqvist M Osterbye T Månsson JE Horn T Buschard K Fredman P 《Glycoconjugate journal》2002,19(6):403-413
Previous studies using pancreas from various mammals and freshly isolated islets from rat pancreas have provided evidence supporting possible involvement of the glycosphingolipid sulfatide in insulin processing and secretion. In this study, sulfatide expression and metabolism in the beta cell line RINr1046-38 (RIN-38), commonly used as a model for beta cell functional studies, were investigated and compared with previous findings from freshly isolated islets. RIN-38 cells expressed similar amounts (2.7 +/- 1.1 nmol/mg protein, n = 19) of sulfatide as isolated rat islets and also followed the same metabolic pathway, mainly through recycling. Moreover, in agreement with findings in isolated islets, the major species of sulfatide isolated from RIN-38 cells contained C16:0 and C24:0 fatty acids. By applying subcellular isolations and electron microscopy and immunocytochemistry techniques, sulfatide was shown to be located to the secretory granules, the plasma membrane and enriched in detergent insoluble microdomains. In the electron microscopy studies, Sulph I staining was also associated with mitochondria and villi structures. In conclusion, RIN-38 cells might be an appropriate model, as a complement to isolated islets where the amount of material often limits the experiments, to further explore the role of sulfatide in insulin secretion and signal transduction of beta cells. 相似文献
86.
Helledie T Jørgensen C Antonius M Krogsdam AM Kratchmarova I Kristiansen K Mandrup S 《Molecular and cellular biochemistry》2002,239(1-2):157-164
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are activated by a number of fatty acids and fatty acid derivatives. By contrast, we have recently shown that acyl-CoA esters display PPAR antagonistic properties in vitro. We have also shown that the adipocyte lipid binding protein (ALBP), the keratinocyte lipid binding protein (KLBP) and the acyl-CoA binding protein (ACBP) exhibit a prominent nuclear localization in differentiating 3T3-L1 adipocytes. Similarly, ectopic expression of these proteins in CV-1 cells resulted in a primarily nuclear localization. We therefore speculated that FABPs and ACBP might regulate the availability of PPAR agonists and antagonists by affecting not only their esterification in the cytoplasm but also their transport to and availability in the nucleus. We show here that coexpression of ALBP or ACBP exerts a negative effect on ligand-dependent PPAR transactivation, when tetradecylthioacetic (TTA) is used as ligand but not when the thiazolidinedione BRL49653 is used as ligand. The results presented here do not support the hypothesis that ALBP facilitates the transport of the fatty acid-type ligands to the nucleus, rather ALBP appears to sequester or increase the turn-over of the agonist. Similarly, our results are in keeping with a model in which ACBP increase the metabolism of these ligands. 相似文献
87.
Escherichia coli RNA polymerase associated with the sigma54 factor (RNAP*sigma54) is a holoenzyme form that transcribes a special class of promoters not recognized by the standard RNA polymerase*sigma70 com plex. Promoters for RNAP*sigma54 vary in their overall 'strength' and show differences in their response to the presence of DNA curvature between enhancer and promoter. In order to examine whether these effects are related to the promoter affinity, we have determined the equilibrium dissociation constant K(d) for the binding of RNAP*sigma54 to the three promoters glnAp2, nifH and nifL. Binding studies were conducted by monitoring the changes in fluorescence anisotropy upon titrating RNAP*sigma54 to carboxyrhodamine-labeled DNA duplexes. For the glnAp2 and nifH promoters similar values of K(d) = 0.94 +/- 0.55 nM and K(d) = 0.85 +/- 0.30 nM were determined at physiological ionic strength, while the nifL promoter displayed a significantly weaker affinity with K(d) = 8.5 +/- 1.9 nM. The logarithmic dependence of K(d) on the ionic strength I was -Deltalog(K(d))/Deltalog(I) = 6.1 +/- 0.5 for the glnAp2, 5.2 +/- 1.2 for the nifH and 2.1 +/- 0.1 for the nifL promoter. This suggests that the polymerase can form fewer ion pairs with the nifL promoter, which would account for its weaker binding affinity. 相似文献
88.
89.
Jenett-Siems K Kraft C Siems K Jakupovic J Solis PN Gupta MP Bienzle U 《Phytochemistry》2003,63(4):377-381
The phytochemical investigation of the leaves of Siparuna pauciflora yielded three novel sesquiterpenoids: the germacrane sipaucin A, the elemane sipaucin B and sipaucin C, comprising a new type of carbon skeleton. In addition, four known aporphine alkaloids-nor-boldine, boldine, laurotetanine, and N-methyl-laurotetanine-were obtained. The evaluation of the antiplasmodial activity of the isolated compounds against two strains of Plasmodium falciparum (PoW, Dd2) showed a moderate activity of nor-boldine. 相似文献
90.
Evariquinone,isoemericellin, and stromemycin from a sponge derived strain of the fungus Emericella variecolor 总被引:2,自引:0,他引:2
From a strain of the fungus Emericella variecolor derived from the marine sponge Haliclona valliculata, two new natural products, evariquinone and isoemericellin, were isolated after HPLC-UV, -MS, and -NMR studies of the extract and their structures were elucidated by mass spectrometry and NMR experiments. Evariquinone showed antiproliferative activity towards KB and NCI-H460 cells at a concentration of 3.16 microg/ml. Furthermore, the fungus was found to produce the known metabolites stromemycin, shamixanthone, and 7-hydroxyemodin. Chemical degradation, NMR decoupling experiments, and spin-system simulation provided evidence for the double bonds in stromemycin to be all E-configured. ROESY experiments established the monosaccharide moiety to be glucose. 相似文献