全文获取类型
收费全文 | 57934篇 |
免费 | 4602篇 |
国内免费 | 4508篇 |
专业分类
67044篇 |
出版年
2024年 | 142篇 |
2023年 | 791篇 |
2022年 | 1855篇 |
2021年 | 3046篇 |
2020年 | 2084篇 |
2019年 | 2506篇 |
2018年 | 2349篇 |
2017年 | 1806篇 |
2016年 | 2548篇 |
2015年 | 3633篇 |
2014年 | 4393篇 |
2013年 | 4444篇 |
2012年 | 5293篇 |
2011年 | 4770篇 |
2010年 | 2885篇 |
2009年 | 2599篇 |
2008年 | 2939篇 |
2007年 | 2641篇 |
2006年 | 2266篇 |
2005年 | 1888篇 |
2004年 | 1511篇 |
2003年 | 1426篇 |
2002年 | 1074篇 |
2001年 | 909篇 |
2000年 | 889篇 |
1999年 | 810篇 |
1998年 | 499篇 |
1997年 | 454篇 |
1996年 | 477篇 |
1995年 | 422篇 |
1994年 | 413篇 |
1993年 | 325篇 |
1992年 | 446篇 |
1991年 | 324篇 |
1990年 | 284篇 |
1989年 | 260篇 |
1988年 | 210篇 |
1987年 | 194篇 |
1986年 | 176篇 |
1985年 | 154篇 |
1984年 | 115篇 |
1983年 | 122篇 |
1982年 | 81篇 |
1981年 | 45篇 |
1980年 | 51篇 |
1979年 | 63篇 |
1976年 | 46篇 |
1974年 | 54篇 |
1973年 | 45篇 |
1972年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
981.
Fu M Liu M Sauve AA Jiao X Zhang X Wu X Powell MJ Yang T Gu W Avantaggiati ML Pattabiraman N Pestell TG Wang F Quong AA Wang C Pestell RG 《Molecular and cellular biology》2006,26(21):8122-8135
The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins. 相似文献
982.
983.
We developed a pharmacophore-based evolutionary approach for virtual screening. This tool, termed the Generic Evolutionary Method for molecular DOCKing (GEMDOCK), combines an evolutionary approach with a new pharmacophore-based scoring function. The former integrates discrete and continuous global search strategies with local search strategies to expedite convergence. The latter, integrating an empirical-based energy function and pharmacological preferences (binding-site pharmacological interactions and ligand preferences), simultaneously serves as the scoring function for both molecular docking and postdocking analyses to improve screening accuracy. We apply pharmacological interaction preferences to select the ligands that form pharmacological interactions with target proteins, and use the ligand preferences to eliminate the ligands that violate the electrostatic or hydrophilic constraints. We assessed the accuracy of our approach using human estrogen receptor (ER) and a ligand database from the comparative studies of Bissantz et al. (J Med Chem 2000;43:4759-4767). Using GEMDOCK, the average goodness-of-hit (GH) score was 0.83 and the average false-positive rate was 0.13% for ER antagonists, and the average GH score was 0.48 and the average false-positive rate was 0.75% for ER agonists. The performance of GEMDOCK was superior to competing methods such as GOLD and DOCK. We found that our pharmacophore-based scoring function indeed was able to reduce the number of false positives; moreover, the resulting pharmacological interactions at the binding site, as well as ligand preferences, were important to the screening accuracy of our experiments. These results suggest that GEMDOCK constitutes a robust tool for virtual database screening. 相似文献
984.
985.
本文从不同年龄、不同地域的银杏叶、茎、根部组织中分离得到20株银杏内共生真菌,经过发酵复筛有5株的产黄酮能力超过5μg/m L。实验对菌株的最佳发酵产黄酮条件进行了优化,优化条件为:3%葡萄糖、0.5%蛋白胨、0.4%酵母膏、0.3%KH2PO4、0.01%Mg SO4·7H2O;起始p H值7.0、最适发酵温度28℃、摇床转速为140 r/min、装液量125 m L/250 m L。在此条件下,该系列菌株在发酵7 d左右产黄酮量可达6.4μg/m L。 相似文献
986.
Ling Li Tanggang Deng Lin Zhang Yanpeng Wang Yangyang Zhou Yan Liu Hui Li Jing Dai Yuan Yang Neng Ling Huimin Liu Jing Liu Lanqin Cao Min Xu Mao Ye 《International journal of biological sciences》2022,18(6):2568
Breast cancer ranks as the most frequently diagnosed cancer among women worldwide. Elevated cytoplasmic p21 levels are often found in breast cancer tissues and related to a poor prognosis. However, the underlying mechanisms that lead to the stabilization of cytoplasmic p21 protein, which normally has a very short half-life, remain obscure. In this study, we found that there was a strong correlation between p21 and USP11 in the cytoplasm of breast cancer tissues and cells. Furthermore, we revealed that ERK1/2 phosphorylated USP11 at the Ser905 site, which promoted the cytoplasmic localization of USP11. In the cytoplasm, USP11 colocalized and interacted with p21. As a result, USP11 catalyzed the removal of polyubiquitin chains bound to cytoplasmic p21 and resulted in its stabilization. Functionally, USP11-mediated stabilization of cytoplasmic p21 induced breast cancer cell proliferation in vitro and in vivo. Our findings provide the first evidence that ubiquitinated p21 in the cytoplasm can be recycled through USP11-mediated deubiquitination, and we identified the USP11-p21 axis in the cytoplasm as a potential therapeutic target for breast cancer control. 相似文献
987.
988.
为了开发利用白酒大曲中的酵母菌资源,采用稀释涂布平板法,从芝麻香型白酒大曲中分离得到15株酵母菌株。利用26S rRNA基因序列分析技术对其进行分类鉴定。结果表明,其中6株酵母菌为酿酒酵母(Saccharomyces cerevisiae),6株为库德里阿兹威氏毕赤酵母(Pichia kudriavzevii),3株为热带假丝酵母(Candida tropicalis);并对代表菌株Y1、Y2及Y4进行了形态观察;最后通过随机扩增多态性DNA标记(random amplified polymorphic DNA, RAPD)对分离得到的酵母菌进行分型,表明6株酿酒酵母分属于5个株型,6株库德里阿兹威氏毕赤酵母分属于5个株型,3株热带假丝酵母分属于3个株型。 相似文献
989.
Combined effect of sodium dodecyl sulfate and enzyme on waste activated sludge hydrolysis and acidification 总被引:4,自引:0,他引:4
Luo K Yang Q Yu J Li XM Yang GJ Xie BX Yang F Zheng W Zeng GM 《Bioresource technology》2011,102(14):7103-7110
The combined effect of sodium dodecyl sulfate (SDS) and enzyme system on hydrolysis and acidification of waste activated sludge (WAS) was investigated. The results showed that the combined system was more effective in the promotion of sludge hydrolysis than sole SDS and sole enzyme, and the SDS + mixed-enzymes (ME) system had better hydrolysis performance than SDS + single enzyme system. Compared with SDS + protease and SDS + amylase systems, the soluble protein concentration in SDS + ME system increased respectively by 20.0% and 44.4%, and the soluble carbohydrate concentration increased by 78.3% and 37.0%, respectively. During the WAS acidification stage, the SDS, ME and SDS + ME system could make the maximum short-chain fatty acids (SCFAs) concentration increased by 1.82 (6th day), 2.04 (5th day), 2.32 (7th day) times, respectively. The composition analysis of SCFAs produced in SDS + ME system indicated that acetic acid was the most prevalent product and propionic acid was the second one. 相似文献
990.
前人已证明人参和三七中富含的达马烷型人参皂甙在通常酸性水解下甙元即发生变化,而在弱酸(如50%醋酸,0.1N盐酸)条件下则形成次级皂甙。本文报道人参甙(ginseno-sides)和三七甙(notoginsenosides)的水溶液在水浴上加热亦分别形成相应的C-20位去糖基的次级皂甙。联系到人参和三七均有在蒸煮加工后C-20位去糖基皂甙收率增大的趋势,似可认为人参和三七中的这类皂甙有相当一部分是在生药的加工泡制以及提取过程中形成的次级皂甙,而不一定是植物体的原生成分。将人参甙Rb_1单体以酸水解,不仅得到主产物人参二醇(3),还分离到异去氢原人参二醇(5)、达马烷-20(22)-烯-3β,12β,26-三醇(6)、20(R)-达马烷-3β,12β,20,25-四醇(7)以及20(S)-和20(R)-原人参二醇(1、2)的混合物,从而认为这些微量成分与人参二醇一样均为达马烷型人参皂甙在酸性水解条件下C-20位糖基断裂后由真甙元的侧链转化形成的工作产物。 相似文献