全文获取类型
收费全文 | 753042篇 |
免费 | 81484篇 |
国内免费 | 354篇 |
专业分类
834880篇 |
出版年
2018年 | 6410篇 |
2016年 | 8475篇 |
2015年 | 11320篇 |
2014年 | 13274篇 |
2013年 | 19958篇 |
2012年 | 21799篇 |
2011年 | 22365篇 |
2010年 | 15114篇 |
2009年 | 14036篇 |
2008年 | 20134篇 |
2007年 | 20785篇 |
2006年 | 19780篇 |
2005年 | 18839篇 |
2004年 | 18848篇 |
2003年 | 18206篇 |
2002年 | 17838篇 |
2001年 | 31965篇 |
2000年 | 32059篇 |
1999年 | 25980篇 |
1998年 | 9377篇 |
1997年 | 9929篇 |
1996年 | 9489篇 |
1995年 | 8757篇 |
1994年 | 8777篇 |
1993年 | 8693篇 |
1992年 | 22417篇 |
1991年 | 21802篇 |
1990年 | 21599篇 |
1989年 | 21522篇 |
1988年 | 19918篇 |
1987年 | 18908篇 |
1986年 | 17600篇 |
1985年 | 18068篇 |
1984年 | 14921篇 |
1983年 | 12887篇 |
1982年 | 9857篇 |
1981年 | 8831篇 |
1980年 | 8414篇 |
1979年 | 14323篇 |
1978年 | 11168篇 |
1977年 | 10317篇 |
1976年 | 9900篇 |
1975年 | 10746篇 |
1974年 | 11528篇 |
1973年 | 11240篇 |
1972年 | 10424篇 |
1971年 | 9357篇 |
1970年 | 8152篇 |
1969年 | 7838篇 |
1968年 | 7222篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
M Hall D K Parker P L Grover J Y Lu N E Hopkins W L Alworth 《Chemico-biological interactions》1990,76(2):181-192
The effects of three aryl acetylenes, 1-ethynylpyrene (EP), 2-ethynylnaphthalene (EN) and 3-ethynylperylene (EPE), upon the metabolism of benzo[a]pyrene (BaP) by microsomes isolated from rat liver were investigated. These aryl acetylenes all inhibited the total metabolism of BaP. Formation of BaP 7,8-dihydrodiol and BaP tetrol products by microsomal preparations from rats that had been pretreated with 3-methylcholanthrene (3MC) were preferentially inhibited. The effects of EP upon the metabolism of BaP 7,8-dihydrodiol by microsomes from rat liver were also studied. This aryl acetylene strongly inhibited the formation of BaP tetrols from BaP 7,8-dihydrodiol by liver microsomes both from untreated rats and from rats pretreated with 3MC, but enhanced the conversion of the BaP dihydrodiol into other metabolites. 相似文献
993.
994.
995.
996.
997.
G C Randall 《Journal of developmental physiology》1988,10(1):77-83
The role of cortisol as a factor controlling the deposition of glycogen in the pig fetus was examined by infusing either a low dose (1 mg/day) or a high dose (3 mg/day) of cortisol into chronically-catheterized hypophysectomized fetal pigs for five days beginning on day 100-104 of gestation. After infusion, liver glycogen was significantly higher (P less than 0.05) and lung glycogen significantly lower (P less than 0.05) than in uninfused hypophysectomized litter mates although concentrations were significantly different from intact litter mates (P less than 0.05). Although skeletal and cardiac muscle content increased after infusion this difference was not significant. Changes in tissue glycogen content were similar for both the low and high rates of infusion. These observations indicate that exogenous cortisol alone is able to stimulate liver glycogen deposition and reverse the effect of hypophysectomy. Although other factors may be necessary for maximal response this suggests that cortisol is an important stimulant for liver glycogen deposition in the fetal pig. The effect of cortisol on muscle glycogen was equivocal suggesting that other hormones may play a more important role in this tissue. 相似文献
998.
Paracoenia fumosalis Cresson previously known only from the USA and Canada is recorded in the Palaearctic Region for the first time. The adults were collected near a thermal hydrosulfuric spring in the Geiser Valley in Kamchatka. A key to species of the genus Paracoenia occurring in Russia is given. 相似文献
999.
Alba Minelli Carmela Conte Silvia Grottelli Ilaria Bellezza Carla Emiliani† Juan P. Bolaños‡ 《Journal of neurochemistry》2009,111(4):956-966
Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes. 相似文献
1000.
Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors
Anne Rietz Dino P. Petrov Matthew Bartolowits Marsha DeSmet V. Jo Davisson Elliot J. Androphy 《PloS one》2016,11(2)
The human papillomavirus (HPV) HPV E6 protein has emerged as a central oncoprotein in HPV-associated cancers in which sustained expression is required for tumor progression. A majority of the E6 protein interactions within the human proteome use an alpha-helix groove interface for binding. The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface. This enables formation of a trimeric complex with p53, resulting in destruction of this tumor suppressor. While recent x-ray crystal structures are useful, examples of small molecule probes that can modulate protein interactions at this interface are limited. To develop insights useful for potential structure-based design of ligands for HPV E6, a series of 2,6-disubstituted benzopyranones were prepared and tested as competitive antagonists of E6-E6AP helix-groove interactions. These small molecule probes were used in both binding and functional assays to evaluate recognition features of the E6 protein. Evidence for an ionic functional group interaction within the helix groove was implicated by the structure-activity among the highest affinity ligands. The molecular topographies of these protein-ligand interactions were evaluated by comparing the binding and activities of single amino acid E6 mutants with the results of molecular dynamic simulations. A group of arginine residues that form a rim-cap over the E6 helix groove offer compensatory roles in binding and recognition of the small molecule probes. The flexibility and impact on the overall helix-groove shape dictated by these residues offer new insights for structure-based targeting of HPV E6. 相似文献