全文获取类型
收费全文 | 3212篇 |
免费 | 225篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 9篇 |
2021年 | 45篇 |
2020年 | 38篇 |
2019年 | 45篇 |
2018年 | 90篇 |
2017年 | 64篇 |
2016年 | 120篇 |
2015年 | 160篇 |
2014年 | 219篇 |
2013年 | 240篇 |
2012年 | 289篇 |
2011年 | 273篇 |
2010年 | 171篇 |
2009年 | 161篇 |
2008年 | 199篇 |
2007年 | 187篇 |
2006年 | 177篇 |
2005年 | 141篇 |
2004年 | 179篇 |
2003年 | 108篇 |
2002年 | 100篇 |
2001年 | 108篇 |
2000年 | 69篇 |
1999年 | 57篇 |
1998年 | 16篇 |
1997年 | 20篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 16篇 |
1991年 | 17篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有3438条查询结果,搜索用时 218 毫秒
991.
Protein tyrosine phosphatase 1B inhibitors from Morus root bark 总被引:2,自引:0,他引:2
Cui L Na M Oh H Bae EY Jeong DG Ryu SE Kim S Kim BY Oh WK Ahn JS 《Bioorganic & medicinal chemistry letters》2006,16(5):1426-1429
An organic layer prepared from the Chinese crude drug 'Sang-Bai-Pi' (Morus root bark) was studied in order to identify the inhibitory compounds for protein tyrosine phosphatase 1B (PTP1B). Bioassay-guided fractionation resulted in the isolation of sanggenon C (1), sanggenon G (2), mulberrofuran C (3) and kuwanon L (4) as PTP1B inhibitors, along with moracin O (5) and moracin P (6). Compounds 1-4 inhibited PTP1B with IC(50) values ranging from 1.6+/-0.3 microM to 16.9+/-1.1 microM. 相似文献
992.
The toxicities of 44 plant essential oils against larvae of Cadra cautella (Walker) were examined using direct contact and vapor phase toxicity bioassays and compared with the lethal activity of chlorpyrifos-methyl, diazinon, dichlorvos, and fenthion, four widely used organophosphorus insecticides. Responses varied according to plant material used and exposure dose and time. In a filter paper contact toxicity bioassay, potent toxicity was produced from buchu leaf, niaouli, and rosemary oils at 2.4 mg/cm2 and armoise, cypress, galbanum, and mace oils at 4.7 mg/cm2. In vapor phase toxicity bioassays with larvae, cypress, galbanum, niaouli, and rosemary oils were much more effective in closed containers than in open containers, indicating that the lethal effects of these oils were largely because of action in the vapor phase. As judged by 24-h LC50 values, potent fumigant action was observed with niaouli oil (64.7 mg/liter air) and rosemary oil (64.6 mg liter/air). Cypress and galbanum oils exhibited weak fumigant activity. These essential oils were less active than dichlorvos (0.86 mg/liter air). Little or no fumigant action was observed with chlorpyrifos-methyl, diazinon, and fenthion. Essential oils described herein, particularly niaouli and rosemary oils, merit further study as potential larvicides for the control of C. cautella. 相似文献
993.
Kim BU Choi J Ahn KH Jeong JK Ha CM Jeong CS Lee CK Kang SG Lee BJ 《Molecules and cells》2006,22(1):30-35
Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter release. The aim of this study was to identify estrogen-dependent expression of Munc18-1 and its role in the regulation of glutamate release for puberty onset. Hypothalamic munc18-1 mRNA levels were significantly increased by estrogen treatment in ovariectomized, immature female rats. During pubertal development, the munc18-1 mRNA levels dramatically increased between the juvenile period and the anestrous phase of puberty. Intracerebroventricular administration of an antisense oligodeoxynucleotide against munc18-1 mRNA significantly decreased glutamate release and delayed the day of puberty onset. These results suggest that Munc18-1, expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release. 相似文献
994.
Salt tolerance was evaluated at the young seedling stage of rice (Oryza sativa L.) using recombinant inbred lines (MG RILs) from a cross between Milyang 23 (japonica/indica) and Gihobyeo (japonica). 22 of 164 MG RILs were classified as tolerant with visual scores of 3.5-5.0 in 0.7% NaCl. Interval mapping of QTLs related to salt tolerance was conducted on the basis of the visual scores at the young seedling stage. Two QTLs, qST1 and qST3, conferring salt tolerance, were detected on chromosome 1 and 3, respectively, and the total phenotypic variance explained by the two QTLs was 36.9% in the MG RIL population. qST1 was the major QTL explaining 27.8% of the total phenotypic variation. qST1 was flanked by Est12-RZ569A, and qST3 was flanked by RG179-RZ596. The detection of new QTLs associated with salt tolerance will provide important information for the functional analysis of rice salt tolerance. 相似文献
995.
Jung HS Kim HS Lee MJ Shin HY Ahn HS Ryu KH Seoh JY Kim CJ Jang JJ 《FEBS letters》2006,580(20):4969-4975
Arsenic trioxide (As(2)O(3)) induces both the differentiation and apoptosis of acute promyelocytic leukemia cells in a concentration dependent manner. We assessed the effects of As(2)O(3) in CADO-ES Ewing's sarcoma (ES), JK-GMS peripheral primitive neuroectodermal tumor (PNET), and SH-SY5Y neuroblastoma cells, as they share common histogenetic backgrounds. As(2)O(3) at low concentrations (0.1-1 microM) induced SH-SY5Y differentiation, and whereas PNET cells acquired a slightly differentiated phenotype, change was minimal in ES cells. Extracellular signal-regulated kinase 2 (ERK2) was activated at low As(2)O(3) concentrations, and PD98059, an inhibitor of MEK-1, blocked SH-SY5Y cell differentiation by As(2)O(3). High concentrations (2-10 microM) of As(2)O(3) induced the apoptosis in all three cell lines, and this was accompanied by the activation of c-jun N-terminal kinase. The generation of H(2)O(2) and activation of caspase 3 were identified as critical components of As(2)O(3)-induced apoptosis in all of the above cell lines. Fibroblast growth factor 2 enhanced As(2)O(3)-induced apoptosis in JK-GMS cells. The overall effects of As(2)O(3) strongly suggest that it has therapeutic potential for the treatment of ES/PNET. 相似文献
996.
Ribosome biogenesis is a cell-essential process that influences cell growth, proliferation, and differentiation. How ribosome biogenesis impacts development, however, is poorly understood. Here, we establish a link between ribosome biogenesis and gonadogenesis in Caenorhabditis elegans that affects germline proliferation and patterning. Previously, we determined that pro-1(+)activity is required in the soma--specifically, the sheath/spermatheca sublineage--to promote normal proliferation and prevent germline tumor formation. Here, we report that PRO-1, like its yeast ortholog IPI3, influences rRNA processing. pro-1 tumors are suppressed by mutations in ncl-1 or lin-35/Rb, both of which elevate pre-rRNA levels. Thus, in this context, lin-35/Rb acts as a soma-autonomous germline tumor promoter. We further report the characterization of two additional genes identified for their germline tumor phenotype, pro-2 and pro-3, and find that they, too, encode orthologs of proteins involved in ribosome biogenesis in yeast (NOC2 and SDA1, respectively). Finally, we demonstrate that depletion of additional C. elegans orthologs of yeast ribosome biogenesis factors display phenotypes similar to depletion of progenes. We conclude that the C. elegans distal sheath is particularly sensitive to alterations in ribosome biogenesis and that ribosome biogenesis defects in one tissue can non-autonomously influence proliferation in an adjacent tissue. 相似文献
997.
Interactions among four proteins encoded by the human cytomegalovirus UL112-113 region regulate their intranuclear targeting and the recruitment of UL44 to prereplication foci 下载免费PDF全文
Four phosphoproteins, of 34, 43, 50, and 84 kDa, with common amino termini are synthesized via alternative splicing from the UL112-113 region of the human cytomegalovirus genome. Although genetic studies provided evidence that both the UL112 and UL113 loci in the viral genome are required for efficient viral replication, whether the four proteins play specific roles or cooperate in replication is not understood. Here we present evidence, using in vitro and in vivo coimmunoprecipitation assays, that the four UL112-113 proteins both self-interact and interact with each other. A mapping study of the 84-kDa protein showed that the N-terminal region encompassing amino acids 1 to 125, which is shared in all UL112-113 proteins and highly conserved among betaherpesviruses, is required for both self-interaction and nuclear localization as foci. Further localization studies revealed that, unlike the 43-, 50-, and 84-kDa proteins, which were distributed as nuclear punctate forms, the 34-kDa form was located predominantly in the cytoplasm. However, when all four proteins were coexpressed simultaneously, all of the UL112-113 proteins were efficiently localized to the promyelocytic leukemia oncogenic domains. We also found that the ability of the UL112-113 proteins to relocate UL44 (the viral polymerase processivity factor) to prereplication foci relied on self-interaction and reached maximal levels when the four proteins were coexpressed. Therefore, our data suggest that interactions occurring among UL112-113 proteins via their shared N-terminal regions are important to both their intranuclear targeting and the recruitment of UL44 to subnuclear sites for viral replication. 相似文献
998.
999.
1000.
Mathivanan S Ahmed M Ahn NG Alexandre H Amanchy R Andrews PC Bader JS Balgley BM Bantscheff M Bennett KL Björling E Blagoev B Bose R Brahmachari SK Burlingame AS Bustelo XR Cagney G Cantin GT Cardasis HL Celis JE Chaerkady R Chu F Cole PA Costello CE Cotter RJ Crockett D DeLany JP De Marzo AM DeSouza LV Deutsch EW Dransfield E Drewes G Droit A Dunn MJ Elenitoba-Johnson K Ewing RM Van Eyk J Faca V Falkner J Fang X Fenselau C Figeys D Gagné P Gelfi C Gevaert K Gimble JM Gnad F Goel R Gromov P 《Nature biotechnology》2008,26(2):164-167