全文获取类型
收费全文 | 11151篇 |
免费 | 19篇 |
国内免费 | 35篇 |
专业分类
系统科学 | 41篇 |
丛书文集 | 205篇 |
教育与普及 | 39篇 |
理论与方法论 | 49篇 |
现状及发展 | 5194篇 |
研究方法 | 496篇 |
综合类 | 5050篇 |
自然研究 | 131篇 |
出版年
2013年 | 97篇 |
2012年 | 167篇 |
2011年 | 296篇 |
2010年 | 67篇 |
2008年 | 189篇 |
2007年 | 213篇 |
2006年 | 204篇 |
2005年 | 232篇 |
2004年 | 188篇 |
2003年 | 191篇 |
2002年 | 202篇 |
2001年 | 287篇 |
2000年 | 294篇 |
1999年 | 190篇 |
1992年 | 176篇 |
1991年 | 149篇 |
1990年 | 155篇 |
1989年 | 158篇 |
1988年 | 166篇 |
1987年 | 157篇 |
1986年 | 168篇 |
1985年 | 229篇 |
1984年 | 140篇 |
1983年 | 141篇 |
1982年 | 98篇 |
1981年 | 118篇 |
1980年 | 152篇 |
1979年 | 383篇 |
1978年 | 282篇 |
1977年 | 304篇 |
1976年 | 219篇 |
1975年 | 220篇 |
1974年 | 340篇 |
1973年 | 280篇 |
1972年 | 299篇 |
1971年 | 308篇 |
1970年 | 420篇 |
1969年 | 364篇 |
1968年 | 368篇 |
1967年 | 336篇 |
1966年 | 292篇 |
1965年 | 214篇 |
1964年 | 71篇 |
1959年 | 117篇 |
1958年 | 211篇 |
1957年 | 169篇 |
1956年 | 160篇 |
1955年 | 132篇 |
1954年 | 132篇 |
1948年 | 104篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
531.
Novel aspects of glypican glycobiology 总被引:5,自引:0,他引:5
Fransson LA Belting M Cheng F Jönsson M Mani K Sandgren S 《Cellular and molecular life sciences : CMLS》2004,61(9):1016-1024
Mutations in glypican genes cause dysmorphic and overgrowth syndromes in men and mice, abnormal development in flies and worms, and defective gastrulation in zebrafish and ascidians. All glypican core proteins share a characteristic pattern of 14 conserved cysteine residues. Upstream from the C-terminal membrane anchorage are 3–4 heparan sulfate attachment sites. Cysteines in glypican-1 can become nitrosylated by nitric oxide in a copper-dependent reaction. When glypican-1 is exposed to ascorbate, nitric oxide is released and participates in deaminative cleavage of heparan sulfate at sites where the glucosamines have a free amino group. This process takes place while glypican-1 recycles via a nonclassical, caveolin-1-associated route. Glypicans are involved in growth factor signalling and transport, e.g. of polyamines. Cargo can be unloaded from heparan sulfate by nitric oxide-dependent degradation. How glypican and its degradation products and the cargo exit from the recycling route is an enigma.Received 27 November 2003; received after revision 8 January 2004; accepted 13 January 2004 相似文献
532.
What’s new in the renin-angiotensin system? 总被引:6,自引:0,他引:6
Chai SY Fernando R Peck G Ye SY Mendelsohn FA Jenkins TA Albiston AL 《Cellular and molecular life sciences : CMLS》2004,61(21):2728-2737
The angiotensin AT(4) receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT(4) receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na(+) transport in isolated renal proximal tubules. The AT(4) receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT(4) receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins. 相似文献
533.
Dynamics of proteins in Golgi membranes: comparisons between mammalian and plant cells highlighted by photobleaching techniques 总被引:5,自引:0,他引:5
In less than a decade the green fluorescent protein (GFP) has become one of the most popular tools for cell biologists for the study of dynamic processes in vivo. GFP has revolutionised the scientific approach for the study of vital organelles, such as the Golgi apparatus. As Golgi proteins can be tagged with GFP, in most cases without altering their targeting and function, it is a great substitute to conventional dyes used in the past to highlight this compartment. In this review, we cover the application of GFP and its spectral derivatives in the study of Golgi dynamics in mammalian and plant cells. In particular, we focus on the technique of selective photobleaching known as fluorescence recovery after photobleaching, which has successfully shed light on essential differences in the biology of the Golgi apparatus in mammalian and plant cells. 相似文献
534.
Vissers LE van Ravenswaaij CM Admiraal R Hurst JA de Vries BB Janssen IM van der Vliet WA Huys EH de Jong PJ Hamel BC Schoenmakers EF Brunner HG Veltman JA van Kessel AG 《Nature genetics》2004,36(9):955-957
CHARGE syndrome is a common cause of congenital anomalies affecting several tissues in a nonrandom fashion. We report a 2.3-Mb de novo overlapping microdeletion on chromosome 8q12 identified by array comparative genomic hybridization in two individuals with CHARGE syndrome. Sequence analysis of genes located in this region detected mutations in the gene CHD7 in 10 of 17 individuals with CHARGE syndrome without microdeletions, accounting for the disease in most affected individuals. 相似文献
535.
The knockout mouse project 总被引:1,自引:0,他引:1
Austin CP Battey JF Bradley A Bucan M Capecchi M Collins FS Dove WF Duyk G Dymecki S Eppig JT Grieder FB Heintz N Hicks G Insel TR Joyner A Koller BH Lloyd KC Magnuson T Moore MW Nagy A Pollock JD Roses AD Sands AT Seed B Skarnes WC Snoddy J Soriano P Stewart DJ Stewart F Stillman B Varmus H Varticovski L Verma IM Vogt TF von Melchner H Witkowski J Woychik RP Wurst W Yancopoulos GD Young SG Zambrowicz B 《Nature genetics》2004,36(9):921-924
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. 相似文献
536.
Davila S Furu L Gharavi AG Tian X Onoe T Qian Q Li A Cai Y Kamath PS King BF Azurmendi PJ Tahvanainen P Kääriäinen H Höckerstedt K Devuyst O Pirson Y Martin RS Lifton RP Tahvanainen E Torres VE Somlo S 《Nature genetics》2004,36(6):575-577
Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease. 相似文献
537.
Gabrielli P Barbante C Plane JM Varga A Hong S Cozzi G Gaspari V Planchon FA Cairns W Ferrari C Crutzen P Cescon P Boutron CF 《Nature》2004,432(7020):1011-1014
An iridium anomaly at the Cretaceous/Tertiary boundary layer has been attributed to an extraterrestrial body that struck the Earth some 65 million years ago. It has been suggested that, during this event, the carrier of iridium was probably a micrometre-sized silicate-enclosed aggregate or the nanophase material of the vaporized impactor. But the fate of platinum-group elements (such as iridium) that regularly enter the atmosphere via ablating meteoroids remains largely unknown. Here we report a record of iridium and platinum fluxes on a climatic-cycle timescale, back to 128,000 years ago, from a Greenland ice core. We find that unexpectedly constant fallout of extraterrestrial matter to Greenland occurred during the Holocene, whereas a greatly enhanced input of terrestrial iridium and platinum masked the cosmic flux in the dust-laden atmosphere of the last glacial age. We suggest that nanometre-sized meteoric smoke particles, formed from the recondensation of ablated meteoroids in the atmosphere at altitudes >70 kilometres, are transported into the winter polar vortices by the mesospheric meridional circulation and are preferentially deposited in the polar ice caps. This implies an average global fallout of 14 +/- 5 kilotons per year of meteoric smoke during the Holocene. 相似文献
538.
The massive star that underwent a collapse of its core to produce supernova (SN)1993J was subsequently identified as a non-variable red supergiant star in images of the galaxy M81 taken before explosion. It showed an excess in ultraviolet and B-band colours, suggesting either the presence of a hot, massive companion star or that it was embedded in an unresolved young stellar association. The spectra of SN1993J underwent a remarkable transformation from the signature of a hydrogen-rich type II supernova to one of a helium-rich (hydrogen-deficient) type Ib. The spectral and photometric peculiarities were best explained by models in which the 13-20 solar mass supergiant had lost almost its entire hydrogen envelope to a close binary companion, producing a 'type IIb' supernova, but the hypothetical massive companion stars for this class of supernovae have so far eluded discovery. Here we report photometric and spectroscopic observations of SN1993J ten years after the explosion. At the position of the fading supernova we detect the unambiguous signature of a massive star: the binary companion to the progenitor. 相似文献
539.
Signal sequences target proteins for secretion from cells or for integration into cell membranes. As nascent proteins emerge from the ribosome, signal sequences are recognized by the signal recognition particle (SRP), which subsequently associates with its receptor (SR). In this complex, the SRP and SR stimulate each other's GTPase activity, and GTP hydrolysis ensures unidirectional targeting of cargo through a translocation pore in the membrane. To define the mechanism of reciprocal activation, we determined the 1.9 A structure of the complex formed between these two GTPases. The two partners form a quasi-two-fold symmetrical heterodimer. Biochemical analysis supports the importance of the extensive interaction surface. Complex formation aligns the two GTP molecules in a symmetrical, composite active site, and the 3'OH groups are essential for association, reciprocal activation and catalysis. This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery. 相似文献
540.