全文获取类型
收费全文 | 17065篇 |
免费 | 52篇 |
国内免费 | 49篇 |
专业分类
系统科学 | 127篇 |
丛书文集 | 181篇 |
教育与普及 | 32篇 |
理论与方法论 | 108篇 |
现状及发展 | 7430篇 |
研究方法 | 861篇 |
综合类 | 8041篇 |
自然研究 | 386篇 |
出版年
2013年 | 142篇 |
2012年 | 328篇 |
2011年 | 649篇 |
2010年 | 136篇 |
2008年 | 361篇 |
2007年 | 346篇 |
2006年 | 372篇 |
2005年 | 383篇 |
2004年 | 361篇 |
2003年 | 322篇 |
2002年 | 309篇 |
2001年 | 481篇 |
2000年 | 457篇 |
1999年 | 331篇 |
1992年 | 285篇 |
1991年 | 213篇 |
1990年 | 233篇 |
1989年 | 229篇 |
1988年 | 227篇 |
1987年 | 223篇 |
1986年 | 215篇 |
1985年 | 309篇 |
1984年 | 250篇 |
1983年 | 170篇 |
1982年 | 186篇 |
1981年 | 175篇 |
1980年 | 189篇 |
1979年 | 458篇 |
1978年 | 342篇 |
1977年 | 349篇 |
1976年 | 323篇 |
1975年 | 348篇 |
1974年 | 424篇 |
1973年 | 404篇 |
1972年 | 416篇 |
1971年 | 469篇 |
1970年 | 610篇 |
1969年 | 518篇 |
1968年 | 555篇 |
1967年 | 496篇 |
1966年 | 432篇 |
1965年 | 325篇 |
1964年 | 129篇 |
1959年 | 184篇 |
1958年 | 309篇 |
1957年 | 209篇 |
1956年 | 196篇 |
1955年 | 156篇 |
1954年 | 188篇 |
1948年 | 146篇 |
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
21.
22.
We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or eradication of this condition. 相似文献
23.
24.
To validate procedures of rational drug design, it is important to develop computational methods that predict binding sites between a protein and a ligand molecule. Many small molecules have been tested using such programs, but examination of protein-protein and peptide-protein interactions has been sparse. We were able to test such applications once the structures of both the maltose-binding protein (MBP) and the ligand-binding domain of the aspartate receptor, which binds MBP, became available. Here we predict the binding site of MBP to its receptor using a 'binary docking' technique in which two MBP octapeptide sequences containing mutations that eliminate maltose chemotaxis are independently docked to the receptor. The peptides in the docked solutions superimpose on their original positions in the structure of MBP and allow the formation of an MBP-receptor complex. The consistency of the computational and biological results supports this approach for predicting protein-protein and peptide-protein interactions. 相似文献
25.
The ability of Enterobacter agglomerans to transform naturally occurring nucleosides into nucleotides has been utilized to transform newly synthesized pyrimidine acyclonucleosides into the corresponding acyclonucleotides. Unselected bacteria were used as the source of nucleoside phosphotransferase, the phosphate group donor being 4-nitrophenyl phosphate in the presence of Zn2+ ions. Optimal reaction conditions are outlined. 相似文献
26.
In myelinated nerves, segregation of voltage-dependent sodium channels to nodes of Ranvier is crucial for saltatory conduction along axons. As sodium channels associate and colocalize with ankyrin at nodes of Ranvier, one possibility is that sodium channels are recruited and immobilized at axonal sites which are specified by the subaxolemmal cytoskeleton, independent of glial cell contact. Alternatively, segregation of channels at distinct sites along the axon may depend on glial cell contact. To resolve this question, we have examined the distribution of sodium channels, ankyrin and spectrin in myelination-competent cocultures of sensory neurons and Schwann cells by immunofluorescence, using sodium channel-, ankyrin- and spectrin-specific antibodies. In the absence of Schwann cells, sodium channels, ankyrin and spectrin are homogeneously distributed on sensory axons. When Schwann cells are introduced into these cultures, the distribution of sodium channels dramatically changes so that channel clusters on axons are abundant, but ankyrin and spectrin remain homogeneously distributed. Addition of latex beads or Schwann cell membranes does not induce channel clustering. Our results suggest that segregation of sodium channels on axons is highly dependent on interactions with active Schwann cells and that continuing axon-glial interactions are necessary to organize and maintain channel distribution during differentiation of myelinated axons. 相似文献
27.
Ana Cuesta Laia Pedrola Teresa Sevilla Javier García-Planells María José Chumillas Fernando Mayordomo Eric LeGuern Ignacio Marín Juan J Vílchez Francesc Palau 《Nature genetics》2002,30(1):22-25
We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes. 相似文献
28.
The failing heart. 总被引:19,自引:0,他引:19
Cardiomyopathies are disorders affecting heart muscle that usually result in inadequate pumping of the heart. They are the most common cause of heart failure and each year kill more than 10,000 people in the United States. In recent years, there have been breakthroughs in understanding the molecular mechanisms involved in this group of conditions, with knowledge of the genetic basis for cardiomyopathies perhaps seeing the largest advance, enabling clinicians to devise improved diagnostic strategies and preparing the stage for new therapies. 相似文献
29.
A calcium sensor in the sodium channel modulates cardiac excitability. 总被引:11,自引:0,他引:11
Hanno L Tan Sabina Kupershmidt Rong Zhang Svetlana Stepanovic Dan M Roden Arthur A M Wilde Mark E Anderson Jeffrey R Balser 《Nature》2002,415(6870):442-447
Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype. 相似文献
30.
A. Fernández-Guasti K. Larsson C. Beyer 《Cellular and molecular life sciences : CMLS》1985,41(11):1414-1416
Summary Intracerebral infusion of (+) bicuculline methiodide, but not of its (–) isomer, in the preoptic area, stimulated masculine sexual behavior in rat as evidenced by a decrease in the number of intromissions preceding ejaculation and a shortening of the ejaculation latency and postejaculatory interval. Data suggest a role of the GABAergic system in mediating masculine sexual behavior.Acknowledgments. Authors wish to thank Ms Elisabeth Wallin for excellent technical assistance and Ms Madelene Kröning for preparing the figures. 相似文献