全文获取类型
收费全文 | 24817篇 |
免费 | 1989篇 |
国内免费 | 1870篇 |
专业分类
28676篇 |
出版年
2024年 | 61篇 |
2023年 | 317篇 |
2022年 | 819篇 |
2021年 | 1331篇 |
2020年 | 900篇 |
2019年 | 1065篇 |
2018年 | 1048篇 |
2017年 | 778篇 |
2016年 | 1095篇 |
2015年 | 1498篇 |
2014年 | 1759篇 |
2013年 | 1922篇 |
2012年 | 2296篇 |
2011年 | 1955篇 |
2010年 | 1194篇 |
2009年 | 1030篇 |
2008年 | 1215篇 |
2007年 | 1080篇 |
2006年 | 927篇 |
2005年 | 813篇 |
2004年 | 697篇 |
2003年 | 633篇 |
2002年 | 546篇 |
2001年 | 482篇 |
2000年 | 417篇 |
1999年 | 403篇 |
1998年 | 255篇 |
1997年 | 269篇 |
1996年 | 260篇 |
1995年 | 243篇 |
1994年 | 221篇 |
1993年 | 137篇 |
1992年 | 209篇 |
1991年 | 146篇 |
1990年 | 131篇 |
1989年 | 109篇 |
1988年 | 73篇 |
1987年 | 94篇 |
1986年 | 56篇 |
1985年 | 56篇 |
1984年 | 43篇 |
1983年 | 30篇 |
1982年 | 30篇 |
1981年 | 19篇 |
1980年 | 8篇 |
1979年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 8 毫秒
121.
Ruihan Zhang Xin Li Zhongjie Liang Kongkai Zhu Junyan Lu Xiangqian Kong Sisheng Ouyang Lin Li Yujun George Zheng Cheng Luo 《PloS one》2013,8(8)
Protein arginine methyltransferase 1 (PRMT1), the major arginine asymmetric dimethylation enzyme in mammals, is emerging as a potential drug target for cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1 will facilitate inhibitor design. However, detailed mechanisms of the methyl transfer process and substrate deprotonation of PRMT1 remain unclear. In this study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation by employing molecular dynamics (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) calculation. Ternary complex models, composed of PRMT1, peptide substrate, and S-adenosyl-methionine (AdoMet) as cofactor, were constructed and verified by 30-ns MD simulation. The snapshots selected from the MD trajectory were applied for the QM/MM calculation. The typical SN2-favored transition states of the first and second methyl transfers were identified from the potential energy profile. Deprotonation of substrate arginine occurs immediately after methyl transfer, and the carboxylate group of E144 acts as proton acceptor. Furthermore, natural bond orbital analysis and electrostatic potential calculation showed that E144 facilitates the charge redistribution during the reaction and reduces the energy barrier. In this study, we propose the detailed mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on the small-molecule effectors design, and enables further investigations into the physiological function of this family. 相似文献
122.
Melanocytes are potential immunocompetent cells: evidence from recognition of immunological characteristics of cultured human melanocytes 总被引:5,自引:0,他引:5
123.
Rhizobia specifically interacts with the host, leguminous plants, leading to the formation of nitrogen-fixing root nodules. The Rhizobium genes essential for nodule formation are called nodulation genes (nod or nol). The expression of nod genes requires the presence of host signals, generally flavonoids, and the product of regulatory nodD gene, NodD[1,2]. The expression of nod genes results in the synthesis of Nod factors, which serve as the signal molecules to elicit root cor-tical cells di… 相似文献
124.
土壤原生动物群落及其生态功能 总被引:8,自引:0,他引:8
土壤原生动物是土壤微生物区系的重要组成部分。在土壤生态系统中 ,由于微生物与微动物的生命活动及其相互作用 ,从而形成了土壤的物质循环和能量转化。土壤原生动物既参与了微生物所介导的物质转化和能量循环 ,又参与了动物对微生物的捕食作用。由于原生动物具有丰富的种类和多样性以及巨大的生物量 ,所以土壤原生动物的群落及其生态功能 ,已引起了人们的广泛关注 ,并且研究理论与方法日益深入。但我国在这方面的研究报道较少 ,本文拟从群落与生态功能方面的进展做一概述。1 土壤原生动物的群落特征土壤与淡水原生动物最早是由Anton… 相似文献
125.
从野皂荚提胶后的副产物中制备分离蛋白 总被引:1,自引:0,他引:1
采用碱提酸沉法从野皂荚提胶后的副产物中制备分离蛋白,研究了制备工艺条件对分离蛋白得率的影响。结果表明:当料液比1∶10~1∶12(m/V)、提取液pH8.0~9.0、浸提温度45~50℃、浸提两次、每次浸提45 m in时,分离蛋白得率可达78.45%。研究结果可为野皂荚提胶副产物中蛋白的综合利用奠定了基础。 相似文献
126.
127.
128.
利用外源性碱性成纤维细胞生长因子(Basic Fibroblast Growth Factor,bFGF)刺激体外培养的人正常牙周膜细胞.采用逆转录-聚合酶链式反应(RT-PCR)检测细胞内decorin的基因表达的变化,研究bFGF对体外培养的人牙周膜细胞内核心蛋白多糖(decorin)的作用,进一步探讨bFGF抑制Ⅰ型胶原的作用机制.发现bFGF刺激牙周膜细胞后能促进牙周膜细胞的增殖,bFGF抑制decorin的合成是bFGF促进牙周膜细胞增殖的重要调节因素之一. 相似文献
129.
Xun Li Junli Wang Jinpei Li Jifeng Wu Yonggang Li Huawei Zhu Ruifang Fan Wenfang Xu 《Bioorganic & medicinal chemistry》2009,17(8):3053-3060
Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2–5 scaffold peptidomimetic compounds. The results demonstrated that most of these l-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC50 values in the micromole range. The structure–activity relationships were also briefly discussed. 相似文献
130.
Jensen KK Previs SF Zhu L Herath K Wang SP Bhat G Hu G Miller PL McLaren DG Shin MK Vogt TF Wang L Wong KK Roddy TP Johns DG Hubbard BK 《American journal of physiology. Endocrinology and metabolism》2012,302(2):E209-E217
The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl-CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received (2)H(2)O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings, (2)H(2)O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered. 相似文献