全文获取类型
收费全文 | 8359篇 |
免费 | 575篇 |
国内免费 | 106篇 |
出版年
2022年 | 73篇 |
2021年 | 157篇 |
2020年 | 73篇 |
2019年 | 95篇 |
2018年 | 115篇 |
2017年 | 92篇 |
2016年 | 139篇 |
2015年 | 209篇 |
2014年 | 254篇 |
2013年 | 406篇 |
2012年 | 448篇 |
2011年 | 434篇 |
2010年 | 259篇 |
2009年 | 246篇 |
2008年 | 305篇 |
2007年 | 325篇 |
2006年 | 313篇 |
2005年 | 282篇 |
2004年 | 249篇 |
2003年 | 245篇 |
2002年 | 258篇 |
2001年 | 195篇 |
2000年 | 200篇 |
1999年 | 170篇 |
1998年 | 82篇 |
1997年 | 85篇 |
1996年 | 80篇 |
1995年 | 76篇 |
1994年 | 74篇 |
1993年 | 72篇 |
1992年 | 178篇 |
1991年 | 159篇 |
1990年 | 159篇 |
1989年 | 145篇 |
1988年 | 124篇 |
1987年 | 144篇 |
1986年 | 123篇 |
1985年 | 155篇 |
1984年 | 147篇 |
1983年 | 145篇 |
1982年 | 110篇 |
1981年 | 92篇 |
1979年 | 136篇 |
1978年 | 95篇 |
1977年 | 100篇 |
1976年 | 76篇 |
1975年 | 90篇 |
1974年 | 91篇 |
1973年 | 85篇 |
1972年 | 96篇 |
排序方式: 共有9040条查询结果,搜索用时 15 毫秒
991.
Protein N-glycosylation requires the presence of asparagine (N) in the consensus tri-peptide NXS/T (where X is any amino acid, S is serine and T is threonine). Several factors affect the glycosylation potential of NXS/T sequons and one such factor is the type of amino acid at position X. While proline was shown to negatively affect N-glycosylation, the nature of other amino acids at this position is not clear. Using Markov chain analysis of tri-peptide NXS/T from viral, archaeal and eukaryotic proteins as well as experimentally confirmed N-glycosylated sequons from eukaryotic proteins, we show here that the occurrence of most sequon types differ significantly from the expected probability. Sequon types with F, G, I, S, T and V amino acids are consistently preferred while those with P and charged amino acids are under-represented in all four groups. Further, proteins contained far fewer number of possible sequon types (maximum 20 types for NXS or NXT taken separately) for any given number of sequons, which may be explained based on random sampling. Consistent with the present finding, majority of the over-represented sequons found in two important viral envelope glycoproteins (hemagglutinin of influenza A H3N2 and glycoprotein120 of HIV-1) are indeed preferred sequon types, which may provide a selective advantage. Accordingly, although there seems to be some preference for sequons, this preference may not be unique to N-glycosylation. 相似文献
992.
Microsatellites are ubiquitous short tandem repeats found in all known genomes and are known to play a very important role in various studies and fields including DNA fingerprinting, paternity studies, evolutionary studies, virulence and adaptation of certain bacteria and viruses etc. Due to the sequencing of several genomes and the availability of enormous amounts of sequence data during the past few years, computational studies of microsatellites are of interest for many researchers. In this context, we developed a software tool called Imperfect Microsatellite Extractor (IMEx), to extract perfect, imperfect and compound microsatellites from genome sequences along with their complete statistics. Recently we developed a user-friendly graphical-interface using JAVA for IMEx to be used as a stand-alone software named G-IMEx. G-IMEx takes a nucleotide sequence as an input and the results are produced in both html and text formats. The Linux version of G-IMEx can be downloaded for free from http://www.cdfd.org.in/imex. 相似文献
993.
994.
995.
James M. Tsay Jean Sippy Damian delToro Benjamin T. Andrews Bonnie Draper Venigalla Rao Carlos E. Catalano Michael Feiss Douglas E. Smith 《The Journal of biological chemistry》2010,285(31):24282-24289
Many double-stranded DNA viruses employ ATP-driven motors to translocate their genomes into small, preformed viral capsids against large forces resisting confinement. Here, we show via direct single-molecule measurements that a mutation T194M downstream of the Walker B motif in the phage λ gpA packaging motor causes an 8-fold reduction in translocation velocity without substantially changing processivity or force dependence, whereas the mutation G212S in the putative C (coupling) motif causes a 3-fold reduction in velocity and a 6-fold reduction in processivity. Meanwhile a T194M pseudorevertant (T194V) showed a near restoration of the wild-type dynamics. Structural comparisons and modeling show that these mutations are in a loop-helix-loop region that positions the key residues of the catalytic motifs, Walker B and C, in the ATPase center and is structurally homologous with analogous regions in chromosome transporters and SF2 RNA helicases. Together with recently published studies of SpoIIIE chromosome transporter and Ded1 RNA helicase mutants, these findings suggest the presence of a structurally conserved region that may be a part of the mechanism that determines motor velocity and processivity in several different types of nucleic acid translocases. 相似文献
996.
George D. Glekas Richard M. Foster Joseph R. Cates Jeffrey A. Estrella Michael J. Wawrzyniak Christopher V. Rao George W. Ordal 《The Journal of biological chemistry》2010,285(3):1870-1878
During chemotaxis toward asparagine by Bacillus subtilis, the ligand is thought to bind to the chemoreceptor McpB on the exterior of the cell and induce a conformational change. This change affects the degree of phosphorylation of the CheA kinase bound to the cytoplasmic region of the receptor. Until recently, the sensing domains of the B. subtilis receptors were thought to be structurally similar to the well studied Escherichia coli four-helical bundle. However, sequence analysis has shown the sensing domains of receptors from these two organisms to be vastly different. Homology modeling of the sensing domain of the B. subtilis asparagine receptor McpB revealed two tandem PAS domains. McpB mutants having alanine substitutions in key arginine and tyrosine residues of the upper PAS domain but not in any residues of the lower PAS domain exhibited a chemotactic defect in both swarm plates and capillary assays. Thus, binding does not appear to occur across any dimeric surface but within a monomer. A modified capillary assay designed to determine the concentration of attractant where chemotaxis is most sensitive showed that when Arg-111, Tyr-121, or Tyr-133 is mutated to an alanine, much more asparagine is required to obtain an active chemoreceptor. Isothermal titration calorimetry experiments on the purified sensing domain showed a KD to asparagine of 14 μm, with the three mutations leading to less efficient binding. Taken together, these results reveal not only a novel chemoreceptor sensing domain architecture but also, possibly, a different mechanism for chemoreceptor activation. 相似文献
997.
Amy C. Schroeder Chuanmei Zhu Srinivasa Rao Yanamadala Rebecca E. Cahoon Kiani A. J. Arkus Leia Wachsstock Jeremy Bleeke Hari B. Krishnan Joseph M. Jez 《The Journal of biological chemistry》2010,285(2):827-834
Aspartate kinase (AK) and homoserine dehydrogenase (HSD) function as key regulatory enzymes at branch points in the aspartate amino acid pathway and are feedback-inhibited by threonine. In plants the biochemical features of AK and bifunctional AK-HSD enzymes have been characterized, but the molecular properties of the monofunctional HSD remain unexamined. To investigate the role of HSD, we have cloned the cDNA and gene encoding the monofunctional HSD (GmHSD) from soybean. Using heterologously expressed and purified GmHSD, initial velocity and product inhibition studies support an ordered bi bi kinetic mechanism in which nicotinamide cofactor binds first and leaves last in the reaction sequence. Threonine inhibition of GmHSD occurs at concentrations (Ki = 160–240 mm) more than 1000-fold above physiological levels. This is in contrast to the two AK-HSD isoforms in soybean that are sensitive to threonine inhibition (Ki∼150 μm). In addition, GmHSD is not inhibited by other aspartate-derived amino acids. The ratio of threonine-resistant to threonine-sensitive HSD activity in soybean tissues varies and likely reflects different demands for amino acid biosynthesis. This is the first cloning and detailed biochemical characterization of a monofunctional feedback-insensitive HSD from any plant. Threonine-resistant HSD offers a useful biotechnology tool for manipulating the aspartate amino acid pathway to increase threonine and methionine production in plants for improved nutritional content. 相似文献
998.
Manjula Karpurapu Dong Wang Dong Van Quyen Tae-Kang Kim Venkatesh Kundumani-Sridharan Srinidhi Pulusani Gadiparthi N. Rao 《The Journal of biological chemistry》2010,285(5):3510-3523
Platelet-derived growth factor BB induced cyclin D1 expression in a time- and nuclear factor of activated T cells (NFAT)-dependent manner in human aortic smooth muscle cells (HASMCs), and blockade of NFATs prevented HASMC DNA synthesis and their cell cycle progression from G1 to S phase. Selective inhibition of NFATc1 by its small interfering RNA also blocked HASMC proliferation and migration. Characterization of the cyclin D1 promoter revealed the presence of several NFAT binding sites, and the site at nucleotide −1333 was found to be sufficient in mediating platelet-derived growth factor BB-induced cyclin D1 promoter-luciferase reporter gene activity. In addition to its role in cell cycle progression, cyclin D1 mediated HASMC migration in an NFATc1-dependent manner. Balloon injury-induced cyclin D1-CDK4 activity requires NFAT activation, and adenovirus-mediated transduction of cyclin D1 was found to be sufficient to overcome the blockade effect of NFATs by VIVIT on balloon injury-induced vascular wall remodeling events, including smooth muscle cell migration from the medial to luminal region, their proliferation in the intimal region, and neointima formation. Together, these results provide more mechanistic evidence for the role of NFATs, particularly NFATc1, in the regulation of HASMC proliferation and migration as well as vascular wall remodeling. NFATc1 could be a potential therapeutic target against the renarrowing of artery after angioplasty. 相似文献
999.
1000.
Maya Schushan Minghui Xiang Pavel Bogomiakov Rajini Rao Nir Ben-Tal 《Journal of molecular biology》2010,396(5):1181-1196
Human NHA2 is a poorly characterized Na+/H+ antiporter recently implicated in essential hypertension. We used a range of computational tools and evolutionary conservation analysis to build and validate a three-dimensional model of NHA2 based on the crystal structure of a distantly related bacterial transporter, NhaA. The model guided mutagenic evaluation of transport function, ion selectivity, and pH dependence of NHA2 by phenotype screening in yeast. We describe a cluster of essential, highly conserved titratable residues located in an assembly region made of two discontinuous helices of inverted topology, each interrupted by an extended chain. Whereas in NhaA, oppositely charged residues compensate for partial dipoles generated within this assembly, in NHA2, polar but uncharged residues suffice. Our findings led to a model for transport mechanism that was compared to the well-known electroneutral NHE1 and electrogenic NhaA subtypes. This study establishes NHA2 as a prototype for the poorly understood, yet ubiquitous, CPA2 antiporter family recently recognized in plants and metazoans and illustrates a structure-driven approach to derive functional information on a newly discovered transporter. 相似文献