全文获取类型
收费全文 | 4539篇 |
免费 | 434篇 |
国内免费 | 290篇 |
专业分类
5263篇 |
出版年
2024年 | 7篇 |
2023年 | 51篇 |
2022年 | 78篇 |
2021年 | 114篇 |
2020年 | 108篇 |
2019年 | 165篇 |
2018年 | 147篇 |
2017年 | 143篇 |
2016年 | 129篇 |
2015年 | 129篇 |
2014年 | 253篇 |
2013年 | 311篇 |
2012年 | 200篇 |
2011年 | 211篇 |
2010年 | 200篇 |
2009年 | 229篇 |
2008年 | 257篇 |
2007年 | 233篇 |
2006年 | 236篇 |
2005年 | 185篇 |
2004年 | 186篇 |
2003年 | 177篇 |
2002年 | 146篇 |
2001年 | 106篇 |
2000年 | 87篇 |
1999年 | 109篇 |
1998年 | 82篇 |
1997年 | 87篇 |
1996年 | 56篇 |
1995年 | 82篇 |
1994年 | 89篇 |
1993年 | 71篇 |
1992年 | 75篇 |
1991年 | 47篇 |
1990年 | 57篇 |
1989年 | 36篇 |
1988年 | 27篇 |
1987年 | 29篇 |
1986年 | 20篇 |
1985年 | 55篇 |
1984年 | 65篇 |
1983年 | 57篇 |
1982年 | 52篇 |
1981年 | 24篇 |
1980年 | 18篇 |
1979年 | 17篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 2篇 |
排序方式: 共有5263条查询结果,搜索用时 15 毫秒
161.
162.
Dalia Rokhsana David M. Dooley Robert K. Szilagyi 《Journal of biological inorganic chemistry》2008,13(3):371-383
A systematic in silico approach has been employed to generate sound, experimentally validated active-site models for galactose oxidase (GO) using a hybrid density functional, B(38HF)P86. GO displays three distinct oxidation states: oxidized [Cu(II)-Y*]; semireduced [Cu(II)-Y]; and reduced [Cu(I)-Y]. Only the [Cu(II)-Y*] and the [Cu(I)-Y] states are assumed to be involved in the catalytic cycle, but their structures have not yet been determined. We have developed several models (1-7) for the [Cu(II)-Y*] state that were evaluated by comparison of our computational results with experimental data. An extended model system (6) that includes solvent molecules and second coordination sphere residues (R330, Y405, and W290) is essential to obtain an experimentally correct electronic structure of the active site. The optimized structure of 6 resulted in a five-coordinate Cu site with a protein radical centered on the Tyr-Cys cofactor. We further validated our converged model with the largest model (7) that included additional outer-sphere residues (Q406, H334, Y329, G513, and T580) and water molecules. Adding these residues did not affect significantly the active site's electronic and geometric structures. Using both 6 and 7, we explored the redox dependence of the active-site structure. We obtained four- and three-coordinate Cu sites for [Cu(II)-Y] and [Cu(I)-Y] states, respectively, that corroborate well with the experimental data. The relative energies of these states were validated by a comparison with experimental redox potentials. Collectively, our computational GO models well reproduce the physicochemical characteristics of the individual states, including their redox behaviors. 相似文献
163.
Identification of resistance gene analogs linked to a powdery mildew resistance locus in grapevine 总被引:12,自引:6,他引:12
Donald TM Pellerone F Adam-Blondon AF Bouquet A Thomas MR Dry IB 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,104(4):610-618
Oligonucleotide primers, designed to conserved regions of nucleotide binding site (NBS) motifs within previously cloned pathogen
resistance genes, were used to amplify resistance gene analogs (RGAs) from grapevine. Twenty eight unique grapevine RGA sequences
were identified and subdivided into 22 groups on the basis of nucleic acid sequence-identity of approximately 70% or greater.
Representatives from each group were used in a bulked segregant analysis strategy to screen for restriction fragment length
polymorphisms linked to the powdery mildew resistance locus, Run1, introgressed into Vitis vinifera L. from the wild grape species Muscadinia rotundifolia. Three RGA markers were found to be tightly linked to the Run1 locus. Of these markers, two (GLP1–12 and MHD145) cosegregated with the resistance phenotype in 167 progeny tested, whereas
the third marker (MHD98) was mapped to a position 2.4 cM from the Run1 locus. The results demonstrate the usefulness of RGA sequences, when used in combination with bulked segregant analysis,
to rapidly generate markers tightly linked to resistance loci in crop species.
Received: 2 May 2001 / Accepted: 3 August 2001 相似文献
164.
Thioredoxin motif of Caenorhabditis elegans PDI-3 provides Cys and His catalytic residues for transglutaminase activity 总被引:1,自引:0,他引:1
Previous reports have suggested that protein disulfide isomerases (PDIs) have transglutaminase (TGase) activity. The structural basis of this reaction has not been revealed. We demonstrate here that Caenorhabditis elegans PDI-3 can function as a Ca(2+)-dependent TGase in assays based on modification of protein- and peptide-bound glutamine residues. By site-directed mutagenesis the second cysteine residue of the -CysGlyHisCys- motif in the thioredoxin domain of the enzyme protein was found to be the active site of the transamidation reaction and chemical modification of histidine in their motif blocked TGase activity. 相似文献
165.
上海广富林地区广富林遗址IT1238和IT0446剖面的孢粉记录,并根据14C数据和遗址层位所建立的年代标尺,通过孢粉分析结果表明,在5300cal.aB.P.之前,本区尚无人类活动的迹象,遗址点周围主要生长由栎树和榆科等植物构成的常绿和落叶阔叶混交林,气候温暖湿润。良渚文化中前期,在花粉谱上出现了农作物的证据,说明当地已有人类进驻,并开展农业活动;大量水生植物花粉的分布说明当时水体面积扩大,降水量增多。良渚文化晚期以后,栎树林几近消失,水生植物减少,而蒿、藜增加,可能是由于水体面积的减少,以及区域气候变得干冷所致。广富林遗存、战国和东汉文化层时期的状况,在一定程度上延续了良渚文化晚期的特征。在战国和东汉文化层时期,栎树林有所恢复,人类活动在后期有所增强。 相似文献
166.
167.
The neuropeptide galanin comes under the powerful and versatile modulators of classical neurotransmitters and is present in brain tissues, which are intimately involved in epileptogenesis. It acts as appealing targets for studying basic mechanisms of seizure initiation and arrest, and for the development of novel approaches for various neurodegenerative diseases. Galanin is widely distributed in the mammalian brain which controls various processes such as sensation of pain, learning, feeding, sexual behaviour, carcinogenesis, pathophysiology of neuroendocrine tumors and others. The function of galanin can be exploited through its interaction with three G-protein coupled receptors subtypes such as GalR1, GalR2 and GalR3. The N-terminal region of galanin comprises about highly conserved 15 amino acid residues, which act as the crucial region for agonist-receptor binding. We have constructed a theoretical structural model for the N-terminal region of galanin from Homo sapiens by homology modeling. The stereochemistry of the model was checked using PROCHECK. The functionally conserved regions were identified by surface mapping of phylogenetic information generated by online web algorithm ConSurf. The docking studies on the pharmacologically important galanin receptors with the theoretical model of N-terminal region of galanin predicted crucial residues for binding which would be useful in the development of novel leads for neurodegenerative disorders. 相似文献
168.
169.
Polar lipids and membrane proteins are major components of biological membranes, both cell membranes and membranes of enveloped viruses. How these two classes of membrane components interact with each other to influence the function of biological membranes is a fundamental question that has attracted intense interest since the origins of the field of membrane studies. One of the most powerful ideas that driven the field is the likelihood that lipids bind to membrane proteins at specific sites, modulating protein structure and function. However only relatively recently has high resolution structure determination of membrane proteins progressed to the point of providing atomic level structure of lipid binding sites on membrane proteins. Analysis of X-ray diffraction, electron crystallography and NMR data over 100 specific lipid binding sites on membrane proteins. These data demonstrate tight lipid binding of both phospholipids and cholesterol to membrane proteins. Membrane lipids bind to membrane proteins by their headgroups, or by their acyl chains, or binding is mediated by the entire lipid molecule. When headgroups bind, binding is stabilized by polar interactions between lipid headgroups and the protein. When acyl chains bind, van der Waals effects dominate as the acyl chains adopt conformations that complement particular sites on the rough protein surface. No generally applicable motifs for binding have yet emerged. Previously published biochemical and biophysical data link this binding with function. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. 相似文献
170.
哺乳动物中原钙粘蛋白(Protocadherin, Pcdh)基因簇包含50多个串联排列的基因,这些基因形成3个紧密相连的基因簇(Pcdhα、Pcdhβ和Pcdhγ),所编码的原钙粘蛋白质群在神经元多样性(Neuronal diversity)和单细胞特异性(Single cell identity)以及神经突触信号转导中发挥重要作用。前期的工作已证实转录因子CTCF(CCCTC-binding factor)与CTCF结合位点(CTCF-binding site, CBS)的方向性结合能够决定增强子和启动子环化的方向以及其远距离交互作用的特异性,并进一步在Pcdh基因座(Locus)形成两个(Pcdhα和Pcdhγ)染色质拓扑结构域(CTCF/cohesin- mediated chromatin domain, CCD),而且染色质拓扑结构域对于控制基因表达调控至关重要。本文通过生物信息学方法对比人类和小鼠序列,发现Pcdhβγ染色质拓扑结构域调控区域中的DNase I超敏位点(DNase I hypersensitive sites, HSs)较为保守。染色质免疫沉淀及大规模测序实验(Chromatin immunoprecipitation and massive parallel sequencing, ChIP-Seq)揭示CBS位点在Pcdhβγ调控区域中成簇分布并且具有相同的方向。凝胶电泳迁移实验(Electrophoresis mobility shift assay, EMSA)确定Pcdhβγ调控区域内具体的42 bp CBS位点并且发现一个CTCF峰包含两个CBS位点。在全基因组范围内,运用计算生物学方法分析CTCF和增强子、启动子等调控元件的关系,发现CBS位点在调控元件附近有较多分布,推测CTCF通过介导增强子和启动子的特异性交互作用,在细胞核三维基因组内形成活性转录枢纽调控基因精准表达。 相似文献