全文获取类型
收费全文 | 16805篇 |
免费 | 34篇 |
国内免费 | 37篇 |
专业分类
系统科学 | 71篇 |
丛书文集 | 263篇 |
教育与普及 | 30篇 |
理论与方法论 | 71篇 |
现状及发展 | 7994篇 |
研究方法 | 693篇 |
综合类 | 7593篇 |
自然研究 | 161篇 |
出版年
2013年 | 76篇 |
2012年 | 185篇 |
2011年 | 364篇 |
2008年 | 222篇 |
2007年 | 243篇 |
2006年 | 279篇 |
2005年 | 270篇 |
2004年 | 376篇 |
2003年 | 254篇 |
2002年 | 254篇 |
2001年 | 479篇 |
2000年 | 442篇 |
1999年 | 326篇 |
1994年 | 74篇 |
1992年 | 286篇 |
1991年 | 221篇 |
1990年 | 238篇 |
1989年 | 235篇 |
1988年 | 202篇 |
1987年 | 234篇 |
1986年 | 278篇 |
1985年 | 335篇 |
1984年 | 230篇 |
1983年 | 226篇 |
1982年 | 205篇 |
1981年 | 217篇 |
1980年 | 224篇 |
1979年 | 563篇 |
1978年 | 475篇 |
1977年 | 437篇 |
1976年 | 341篇 |
1975年 | 404篇 |
1974年 | 564篇 |
1973年 | 452篇 |
1972年 | 472篇 |
1971年 | 553篇 |
1970年 | 696篇 |
1969年 | 538篇 |
1968年 | 539篇 |
1967年 | 536篇 |
1966年 | 430篇 |
1965年 | 371篇 |
1964年 | 121篇 |
1959年 | 193篇 |
1958年 | 331篇 |
1957年 | 247篇 |
1956年 | 191篇 |
1955年 | 192篇 |
1954年 | 190篇 |
1948年 | 127篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
341.
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
342.
A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. 总被引:59,自引:0,他引:59
G J Farrar P Kenna S A Jordan R Kumar-Singh M M Humphries E M Sharp D M Sheils P Humphries 《Nature》1991,354(6353):478-480
The group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000. We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q, close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP. Another adRP gene has been mapped to chromosome 8p. A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p, showing tight linkage with the gene for peripherin, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmembrane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa. 相似文献
343.
344.
A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin 总被引:76,自引:0,他引:76
T Serafini G Stenbeck A Brecht F Lottspeich L Orci J E Rothman F T Wieland 《Nature》1991,349(6306):215-220
Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A. 相似文献
345.
New use of BCG for recombinant vaccines 总被引:147,自引:0,他引:147
C K Stover V F de la Cruz T R Fuerst J E Burlein L A Benson L T Bennett G P Bansal J F Young M H Lee G F Hatfull 《Nature》1991,351(6326):456-460
BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice. 相似文献
346.
A novel cyclin encoded by a bcl1-linked candidate oncogene 总被引:145,自引:0,他引:145
T Motokura T Bloom H G Kim H Jüppner J V Ruderman H M Kronenberg A Arnold 《Nature》1991,350(6318):512-515
We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13. 相似文献
347.
Arginine vasopressin enhances pHi regulation in the presence of HCO3- by stimulating three acid-base transport systems 总被引:14,自引:0,他引:14
Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi increase is a necessary signal for mitogenesis. In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts. In mesangial cells, arginine vasopressin (AVP) raises pHi in the absence of HCO3-, but lowers it when HCO3- is present; growth is stimulated under both conditions. We report here that, in the presence of HCO3-, AVP stimulates two potent HCO3- transporters, as well as the Na+/H+ exchanger. These are the Na+-dependent and Na+-independent Cl-/HCO3- exchangers. Our results indicate that AVP causes acidification in the presence of HCO3- because, at the resting pHi, it stimulates Na+-independent Cl-/HCO3- exchange (which lowers pHi) more than it stimulates the sum of Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange (both of which raise pHi). The stimulation of three acid-base transporters by the growth factor AVP greatly enhances the ability of the cell to regulate pHi. 相似文献
348.
Retinoic acid regulates growth hormone gene expression 总被引:16,自引:0,他引:16
349.
Putative transcription activator with alternative isoforms encoded by human ZFX gene 总被引:9,自引:0,他引:9
A Schneider-G?dicke P Beer-Romero L G Brown G Mardon S W Luoh D C Page 《Nature》1989,342(6250):708-711
350.
Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells 总被引:47,自引:0,他引:47
Tolerance to self-antigens has been shown to develop during ontogeny as a result of the clonal deletion of self-reactive T cells. Tolerance, or better 'nonresponsiveness', to specific antigens can also be induced in adult animals but the mechanism(s) involved are not well understood. Most murine T-helper cells that express the V beta 6 T-cell receptor gene segment are specific for Mls-1a antigens. We have therefore been able to use an anti-V beta 6 monoclonal antibody to follow the fate of Mls-1a specific T cells in adult Mls-1b mice made specifically unresponsive to Mls-1a. We show that the induced unresponsiveness is not due to clonal deletion, but rather to clonal anergy. The anergic V beta 6 T-helper cells express IL-2 receptors and undergo limited blastogenesis in vitro upon stimulation, but do not produce IL-2, in marked contrast to V beta 6 cells from naive mice. Our data appear to represent an in vivo correlate for the induction of anergy that has been observed in T-cell lines in vitro. 相似文献