全文获取类型
收费全文 | 27608篇 |
免费 | 98篇 |
国内免费 | 111篇 |
专业分类
系统科学 | 121篇 |
丛书文集 | 451篇 |
教育与普及 | 36篇 |
理论与方法论 | 91篇 |
现状及发展 | 12109篇 |
研究方法 | 1272篇 |
综合类 | 13268篇 |
自然研究 | 469篇 |
出版年
2013年 | 214篇 |
2012年 | 423篇 |
2011年 | 891篇 |
2010年 | 174篇 |
2008年 | 489篇 |
2007年 | 601篇 |
2006年 | 536篇 |
2005年 | 569篇 |
2004年 | 616篇 |
2003年 | 498篇 |
2002年 | 538篇 |
2001年 | 861篇 |
2000年 | 825篇 |
1999年 | 586篇 |
1992年 | 556篇 |
1991年 | 386篇 |
1990年 | 421篇 |
1989年 | 406篇 |
1988年 | 403篇 |
1987年 | 413篇 |
1986年 | 455篇 |
1985年 | 581篇 |
1984年 | 403篇 |
1983年 | 334篇 |
1982年 | 295篇 |
1981年 | 321篇 |
1980年 | 370篇 |
1979年 | 869篇 |
1978年 | 678篇 |
1977年 | 653篇 |
1976年 | 522篇 |
1975年 | 516篇 |
1974年 | 770篇 |
1973年 | 639篇 |
1972年 | 704篇 |
1971年 | 764篇 |
1970年 | 1073篇 |
1969年 | 840篇 |
1968年 | 723篇 |
1967年 | 747篇 |
1966年 | 710篇 |
1965年 | 529篇 |
1964年 | 180篇 |
1959年 | 267篇 |
1958年 | 525篇 |
1957年 | 361篇 |
1956年 | 279篇 |
1955年 | 255篇 |
1954年 | 297篇 |
1948年 | 186篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Ion transport proteins must remove an ion's hydration shell to coordinate the ion selectively on the basis of its size and charge. To discover how the K+ channel solves this fundamental aspect of ion conduction, we solved the structure of the KcsA K+ channel in complex with a monoclonal Fab antibody fragment at 2.0 A resolution. Here we show how the K+ channel displaces water molecules around an ion at its extracellular entryway, and how it holds a K+ ion in a square antiprism of water molecules in a cavity near its intracellular entryway. Carbonyl oxygen atoms within the selectivity filter form a very similar square antiprism around each K+ binding site, as if to mimic the waters of hydration. The selectivity filter changes its ion coordination structure in low K+ solutions. This structural change is crucial to the operation of the selectivity filter in the cellular context, where the K+ ion concentration near the selectivity filter varies in response to channel gating. 相似文献
952.
夏提姑丽·阿不都热依木 《中国西部科技》2009,8(15):47-48
公路基本建设事业的快速发展,对公路养护工程提出了更高的要求,公路养护不断遇到新的难题,面对困难和挑战。文章结合本地区公路养护实际工作实践,对公路养护管理存在的问题进行了分析,并探讨了相应对策。 相似文献
953.
本文建立了同时考虑轴颈径向位移和歪斜时的滑动轴承动力学模型.对于这种模型,油膜力将扩展为四个广义力分量.文章将相应的动力系数矩阵分解为对称和反对称两部分并讨论其物理性质.然后,本文推导得出该模型的正交变换矩阵,在此基础上导得各向同性的动力系数矩阵表达式,并讨论了诸元素的物理意义.文章最后引入动力系数椭圆的概念以分析非对称动力系数矩阵的变换性质. 相似文献
954.
Self peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive and in negative selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae detects the MHC class II bound form of a major self peptide. Y-Ae binds approximately 12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells that drive positive selection, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection. 相似文献
955.
956.
Homeobox gene expression correlated with the bifurcation process of limb cartilage development. 总被引:9,自引:0,他引:9
The complex architecture of the limb cartilage pattern probably develops by the sequential segmentation and branching process of precartilaginous cell condensation under the control of positional signalling provided by the zone of polarizing activity (anteroposterior) and the apical ectodermal ridge (proximodistal). This signalling is monitored and interpreted in the mesenchymal cells and induces the position-specific response of subsets of genes. Homeobox genes may be responsible for the interpretation of signalling. A correlation between limb pattern and expression domains of the homeobox genes in the upstream region of Hox/Chox-4 has been proposed. We have analysed the spatial expression pattern of the Chox-1 genes during development of chick limb buds. In contrast to genes in Hox/Chox-4 expressed coordinately along the anteroposterior axis, homeobox genes in Chox-1 have unique and mutually exclusive expression domains along the proximodistal axis. We report here that the expression domains of the Chox-1 genes are closely related to the segmental structure of cartilage along the proximodistal axis, whereas the expression domains of the Chox-4 genes are related to the cartilage branching pattern. 相似文献
957.
The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current. 相似文献
958.
The amino acids L-glutamic and L-aspartic acids form the most widespread excitatory transmitter network in mammalian brain. The excitation produced by L-glutamic acid is important in the early development of the nervous system, synaptic plasticity and memory formation, seizures and neuronal degeneration. The receptors activated by L-glutamic acid are a target for therapeutic intervention in neurodegenerative diseases, brain ischaemia and epilepsy. There are two types of receptors for the excitatory amino acids, those that lead to the opening of cation-selective channels and those that activate phospholipase C (ref. 11). The receptors activating ion channels are NMDA (N-methyl-D-aspartate) and kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive receptors. The complementary DNAs for the kainate/AMPA receptor and for the metabotropic receptor have been cloned. We report here on the isolation and characterization of a protein complex of four major proteins that represents an intact complex of the NMDA receptor ion channel and on the cloning of the cDNA for one of the subunits of this receptor complex, the glutamate-binding protein. 相似文献
959.
W Dalemans P Barbry G Champigny S Jallat K Dott D Dreyer R G Crystal A Pavirani J P Lecocq M Lazdunski 《Nature》1991,354(6354):526-528
Cystic fibrosis is associated with a defect in epithelial chloride ion transport which is caused by mutations in a membrane protein called CFTR (cystic fibrosis transmembrane conductance regulator). Heterologous expression of CFTR produces cyclicAMP-sensitive Cl(-)-channel activity. Deletion of phenylalanine at amino-acid position 508 in CFTR (delta F508 CFTR) is the most common mutation in cystic fibrosis. It has been proposed that this mutation prevents glycoprotein maturation and its transport to its normal cellular location. We have expressed both CFTR and delta F508 CFTR in Vero cells using recombinant vaccinia virus. Although far less delta F508 CFTR reached the plasma membrane than normal CFTR, sufficient delta F508 CFTR was expressed at the plasma membrane to permit functional analysis. delta F508 CFTR expression induced a reduced activity of the cAMP-activated Cl- channel, with conductance, anion selectivity and open-time kinetics similar to those of CFTR, but with much greater closed times, resulting in a large decrease of open probability. The delta F508 mutation thus seems to have two major consequences, an abnormal translocation of the CFTR protein which limits membrane insertion, and an abnormal function in mediating Cl- transport. 相似文献
960.
F Revah D Bertrand J L Galzi A Devillers-Thiéry C Mulle N Hussy S Bertrand M Ballivet J P Changeux 《Nature》1991,353(6347):846-849
A variety of ligand-gated ion channels undergo a fast activation process after the rapid application of agonist and also a slower transition towards desensitized or inactivated closed channel states when exposure to agonist is prolonged. Desensitization involves at least two distinct closed states in the acetylcholine receptor, each with an affinity for agonists higher than those of the resting or active conformations. Here we investigate how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7 receptor, using site-directed mutagenesis and expression in Xenopus oocytes. Mutations of the highly conserved leucine 247 residue from the uncharged MII segment of alpha 7 suppress inhibition by the open-channel blocker QX-222, indicating that this residue, like others from MII, faces the lumen of the channel. But, unexpectedly, the same mutations decrease the rate of desensitization of the response, increase the apparent affinity for acetylcholine and abolish current rectification. Moreover, unlike wild-type alpha 7, which has channels with a single conductance level, the leucine-to-threonine mutant has an additional conducting state active at low acetylcholine concentrations. It is possible that mutation of Leu 247 renders conductive one of the high-affinity desensitized states of the receptor. 相似文献