全文获取类型
收费全文 | 9845篇 |
免费 | 836篇 |
国内免费 | 763篇 |
专业分类
11444篇 |
出版年
2024年 | 30篇 |
2023年 | 135篇 |
2022年 | 285篇 |
2021年 | 411篇 |
2020年 | 289篇 |
2019年 | 351篇 |
2018年 | 376篇 |
2017年 | 272篇 |
2016年 | 376篇 |
2015年 | 607篇 |
2014年 | 640篇 |
2013年 | 697篇 |
2012年 | 867篇 |
2011年 | 777篇 |
2010年 | 485篇 |
2009年 | 425篇 |
2008年 | 463篇 |
2007年 | 512篇 |
2006年 | 457篇 |
2005年 | 360篇 |
2004年 | 316篇 |
2003年 | 314篇 |
2002年 | 272篇 |
2001年 | 211篇 |
2000年 | 173篇 |
1999年 | 131篇 |
1998年 | 87篇 |
1997年 | 99篇 |
1996年 | 76篇 |
1995年 | 79篇 |
1994年 | 79篇 |
1993年 | 59篇 |
1992年 | 91篇 |
1991年 | 59篇 |
1990年 | 77篇 |
1989年 | 78篇 |
1988年 | 45篇 |
1987年 | 37篇 |
1986年 | 46篇 |
1985年 | 38篇 |
1984年 | 23篇 |
1983年 | 30篇 |
1982年 | 17篇 |
1981年 | 17篇 |
1980年 | 20篇 |
1979年 | 17篇 |
1975年 | 13篇 |
1974年 | 13篇 |
1973年 | 14篇 |
1971年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
41.
Autonomously folding beta-hairpins have recently emerged as powerful tools for elucidating the origins of antiparallel beta-sheet folding preferences. Analysis of such model systems has suggested four potential sources of beta-sheet stability: (1) the conformational propensity of the loop segment that connects adjacent strands; (2) favorable contacts between side-chains on adjacent strands; (3) interstrand hydrogen bonds; and (4) the intrinsic beta-sheet propensities of the strand residues. We describe the design and analysis of a series of isomeric 20 residue peptides in which factors (1)-(4) are identical. Differences in beta-hairpin formation within this series demonstrate that these four factors, individually, are not sufficient to explain beta-sheet stability. In agreement with the prediction of a simple statistical mechanical model for beta-hairpin formation, our results show that the separation between the loop segment and an interstrand cluster of hydrophobic side-chains strongly influences beta-hairpin size and stability, with a smaller separation leading to greater stability. 相似文献
42.
汉族马凡综合征(MFS)患者FBN1基因两种新发突变分析 总被引:1,自引:0,他引:1
为调查马凡综合征(Marfan syndrome, MFS)患者的原纤维蛋白-1(Fibrillin-1, FBN1)基因突变情况, 应用聚合酶链反应(PCR)和变性高效液相色谱法(Denaturing high-performance liquid chromatography, DHPLC)对MFS患者的FBN1基因进行突变筛查, 对DHPLC初筛异常的DNA片段进行测序分析。结果在两个MFS家系中发现FBN1基因两种新的突变: 一种为复合突变包含第55号外显子的缺失突变c.6862_6871delGGCTGTGTAG (p.Gly2288MetfsX109)、同义突变c.6861A>G和内含子的突变c.[6871+1_6871+11delGTAAGAGGATC; 6871+34dupCATCAGAAGTGACAGTGGACA]; 另一种为第20号外显子的错义突变c.2462G>A(p.Cys821Tyr)。研究表明, FBN1基因的缺失突变c.[6862_6871delGGCTGTGTAG; 6871+1_6871+11delGTAAGAGGATC] (p.Gly2288MetfsX109)和错义突变c.2462G>A(p.Cys821Tyr)可能分别是这两个家系患者的致病原因。 相似文献
43.
Ping Xu Yangxi Zheng Jiujiang Liao Mingyu Hu Yike Yang Baozhen Zhang Mark D. Kilby Huijia Fu Yamin Liu Fumei Zhang Liling Xiong Xiyao Liu Huili Jin Yue Wu Jiayu Huang Tingli Han Li Wen Rufei Gao Yong Fu Xiujun Fan Hongbo Qi Philip N. Baker Chao Tong 《Cell proliferation》2023,56(2)
Pre‐eclampsia (PE) is deemed an ischemia‐induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography–mass spectrometry (GC–MS). Trophoblast‐specific AMPKα1‐deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle‐delivered A769662. Trophoblast glucose uptake was measured by 2‐NBDG and 2‐deoxy‐d‐[3H] glucose uptake assays. Cellular metabolism was investigated by the Seahorse assay and GC–MS.PE complicated trophoblasts are associated with AMPK hyperactivation due not to energy deficiency. Thereafter, AMPK activation during placentation exacerbated PE manifestations but alleviated cell death in the placenta. AMPK activation in trophoblasts contributed to GLUT3 translocation and subsequent glucose metabolism, which were redirected into gluconeogenesis, resulting in deposition of glycogen and accumulation of phosphoenolpyruvate; the latter enhanced viability but compromised trophoblast invasion. However, ablation of AMPK in the mouse placenta resulted in decreased glycogen deposition and structural malformation. These data reveal a novel homeostasis between invasiveness and viability in trophoblasts, which is mechanistically relevant for switching between the ‘go’ and ‘grow’ cellular programs.Pre‐eclampsia (PE) is associated with trophoblast AMPK hyperactivation, presumably due to LKB1 phosphorylation, and glucose uptake is consequently increased via trafficking of GLUT3 from the cytosol to the plasma membrane. Such translocation enhances glycolytic flux and redirects glucose metabolic intermediates into gluconeogenesis, resulting in PEP accumulation, which not only benefits cell survival but also suppresses invasion by repressing MMPs, and thus in turn modulates switching between the ‘go’ and ‘grow’ cellular programs. 相似文献
44.
45.
46.
47.
48.
Maureen K. Purcell Jian-Long Mu David C. Higgins Ramu Elango Harry Whitmore Stephen Harris Beverly Paigen 《Mammalian genome》2001,12(7):495-500
Ath6 is a novel quantitative trait locus associated with differences in susceptibility to atherosclerosis between C57BL/6J (B6)
and C57BLKS/J (BKS) inbred mouse strains. Combining data from an intercross and a backcross (1593 meioses) between mice from
B6 and BKS strains and from The Jackson Laboratory interspecific backcross panels, (C57BL/6J ×Mus spretus) F1× C57BL/6J and (C57BL/6J × SPRET/Ei) F1× SPRET/Ei, we constructed a consensus genetic map and narrowed Ath6 to a 1.07 ± 0.26 cM interval between the anonymous DNA marker D12Pgn4 and the gene Nmyc1. This region is near the proximal end of murine Chromosome (Chr) 12, which is homologous to the human chromosomal region 2p24-p25.
Marker order in the Ath6 region was concordant among the two crosses and The Jackson Laboratory interspecific backcross panels. This high resolution
map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17. The two Ath6 crosses have a combined potential resolution of 0.06 cM.
Received: 12 September 2000 / Accepted: 22 February 2001 相似文献
49.
Grijota Francisco Javier Muñoz Diego Bartolomé Ignacio Siquier-Coll Jesús Robles María Concepción Maynar Marcos 《Biological trace element research》2020,195(1):39-45
Biological Trace Element Research - The aim of the present study was to determine changes occurring in the erythrocyte concentrations of arsenic (As), cadmium (Cd) and lead (Pb) in highly trained... 相似文献
50.
Construction of a recombinant BHV-1 expressing the VP1 gene of foot and mouth disease virus and its immunogenicity in a rabbit model 总被引:1,自引:0,他引:1
Xian-Gang Ren Fei Xue Yuan-Mao Zhu Guang-Zhi Tong Yan-Hui Wang Jun-Ke Feng Hong-Fei Shi Yu-Ran Gao 《Biotechnology letters》2009,31(8):1159-1165
Foot-and-mouth disease (FMD) and infectious bovine rhinotracheitis (IBR) are two important infectious diseases of cattle.
Using bovine herpesvirus type 1 (BHV-1) as a gene delivery vector for development of live-viral vaccines has gained widespread
interest. In this study, a recombinant BHV-1 was constructed by inserting the synthetic FMDV (O/China/99) VP1 gene in the
the gE locus of BHV-1 genome under the control of immediately early gene promoter of human cytomegalovirus (phIE CMV) and
bovine growth hormone polyadenylation (BGH polyA) signal. After homologous recombination and plaque purification, a recombinant
virus named BHV-1/gE−/VP1 was acquired and identified. The immunogenicity was confirmed in a rabbit model by virus neutralization test and enzyme-linked
immunosorbent assay (ELISA). The result indicated that the BHV-1/gE−/VP1 has the potential for being developed as a bivalent vaccine for FMD and IBR. 相似文献