全文获取类型
收费全文 | 34166篇 |
免费 | 90篇 |
国内免费 | 89篇 |
专业分类
系统科学 | 283篇 |
丛书文集 | 591篇 |
教育与普及 | 73篇 |
理论与方法论 | 110篇 |
现状及发展 | 13988篇 |
研究方法 | 1307篇 |
综合类 | 17346篇 |
自然研究 | 647篇 |
出版年
2013年 | 268篇 |
2012年 | 431篇 |
2011年 | 1092篇 |
2010年 | 185篇 |
2008年 | 516篇 |
2007年 | 617篇 |
2006年 | 629篇 |
2005年 | 614篇 |
2004年 | 597篇 |
2003年 | 589篇 |
2002年 | 523篇 |
2001年 | 1189篇 |
2000年 | 1131篇 |
1999年 | 635篇 |
1992年 | 638篇 |
1991年 | 549篇 |
1990年 | 575篇 |
1989年 | 530篇 |
1988年 | 541篇 |
1987年 | 527篇 |
1986年 | 536篇 |
1985年 | 681篇 |
1984年 | 537篇 |
1983年 | 473篇 |
1982年 | 389篇 |
1981年 | 392篇 |
1980年 | 488篇 |
1979年 | 1050篇 |
1978年 | 860篇 |
1977年 | 801篇 |
1976年 | 687篇 |
1975年 | 797篇 |
1974年 | 1029篇 |
1973年 | 864篇 |
1972年 | 896篇 |
1971年 | 1066篇 |
1970年 | 1370篇 |
1969年 | 1030篇 |
1968年 | 989篇 |
1967年 | 948篇 |
1966年 | 897篇 |
1965年 | 636篇 |
1964年 | 153篇 |
1959年 | 375篇 |
1958年 | 588篇 |
1957年 | 438篇 |
1956年 | 365篇 |
1955年 | 340篇 |
1954年 | 354篇 |
1948年 | 248篇 |
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
931.
The peroxisomal membrane protein, with a relative molecular mass of 70,000 (M(r) 70K) (PMP70), is an important component of peroxisomal membranes and an ATP-binding cassette protein. To investigate its possible involvement in Zellweger syndrome (ZS), an inborn error of peroxisome assembly, we cloned and sequenced cDNAs for human PMP70 and mapped the gene to chromosome 1. Amongst 32 probands with ZS or related disorders, we found two mutant PMP70 alleles in single ZS probands from the same complementation group. One allele has a donor splice site mutation and the second a missense mutation. Our results suggest that PMP70 plays an important role in peroxisome biogenesis and that mutations in PMP70 may be responsible for a subset of ZS patients. 相似文献
932.
A survey of expressed genes in Caenorhabditis elegans. 总被引:29,自引:0,他引:29
R Waterston C Martin M Craxton C Huynh A Coulson L Hillier R Durbin P Green R Shownkeen N Halloran 《Nature genetics》1992,1(2):114-123
As an adjunct to the genomic sequencing of Caenorhabditis elegans, we have investigated a representative cDNA library of 1,517 clones. A single sequence read has been obtained from the 5' end of each clone, allowing its characterization with respect to the public databases, and the clones are being localized on the genome map. The result is the identification of about 1,200 of the estimated 15,000 genes of C. elegans. More than 30% of the inferred protein sequences have significant similarity to existing sequences in the databases, providing a route towards in vivo analysis of known genes in the nematode. These clones also provide material for assessing the accuracy of predicted exons and splicing patterns and will lead to a more accurate estimate of the total number of genes in the organism than has hitherto been available. 相似文献
933.
Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues. 总被引:16,自引:0,他引:16
W R McCombie M D Adams J M Kelley M G FitzGerald T R Utterback M Khan M Dubnick A R Kerlavage J C Venter C Fields 《Nature genetics》1992,1(2):124-131
A database containing mapped partial cDNA sequences from Caenorhabditis elegans will provide a ready starting point for identifying nematode homologues of important human genes and determining their functions in C. elegans. A total of 720 expressed sequence tags (ESTs) have been generated from 585 clones randomly selected from a mixed-stage C. elegans cDNA library. Comparison of these ESTs with sequence databases identified 422 new C. elegans genes, of which 317 are not similar to any sequences in the database. Twenty-six new genes have been mapped by YAC clone hybridization. Members of several gene families, including cuticle collagens, GTP-binding proteins, and RNA helicases were discovered. Many of the new genes are similar to known or potential human disease genes, including CFTR and the LDL receptor. 相似文献
934.
V Timmerman E Nelis W Van Hul B W Nieuwenhuijsen K L Chen S Wang K Ben Othman B Cullen R J Leach C O Hanemann 《Nature genetics》1992,1(3):171-175
Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy. 相似文献
935.
Isolation of a candidate gene for Norrie disease by positional cloning. 总被引:17,自引:0,他引:17
W Berger A Meindl T J van de Pol F P Cremers H H Ropers C D?erner A Monaco A A Bergen R Lebo M Warburg 《Nature genetics》1992,1(3):199-203
The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein. 相似文献
936.
D Sidransky T Mikkelsen K Schwechheimer M L Rosenblum W Cavanee B Vogelstein 《Nature》1992,355(6363):846-847
Tumour progression is a fundamental feature of the biology of cancer. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomas). To define the genetic events underlying brain tumour progression, we analysed the p53 gene in ten primary brain tumour pairs. Seven pairs consisted of tumours that were high grade both at presentation and recurrence (group A) and three pairs consisted of low-grade tumours that had progressed to higher grade tumours (group B). In group A pairs, four of the recurrent tumours contained a p53 gene mutation; in three of them, the same mutation was found in the primary tumour. In group B pairs, progression to high grade was associated with a p53 gene mutation. A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma. Thus, the histological progression of brain tumours was associated with a clonal expansion of cells that had previously acquired a mutation in the p53 gene, endowing them with a selective growth advantage. These experimental observations strongly support Nowell's clonal evolution model of tumour progression. 相似文献
937.
Dynamin was initially identified in calf brain tissue as a protein of relative molecular mass 100,000 which induced nucleotide-sensitive bundling of microtubules. Purified dynamin showed only trace ATPase activity. But in combination with an activating factor removed during the purification, it exhibited microtubule-activated ATPase activity and dynamin-induced bundles showed evidence of ATP-dependent force production. Dynamin is the product of the Drosophila gene shibire, which has been implicated in synaptic vesicle recycling and, more generally, in the budding of endocytic vesicles from the plasma membrane. Dynamin also shows extensive homology with proteins that participate in vacuolar protein sorting and spindle pole-body separation in yeast, and in interferon-induced viral resistance in mammals. All members of this family contain consensus sequence elements consistent with GTP binding near their amino termini, although none has been shown to have GTPase activity. We report here that dynamin is a specific GTPase which can be stimulated to very high levels of activity by microtubules. 相似文献
938.
939.
940.
Human aminopeptidase N is a receptor for human coronavirus 229E. 总被引:62,自引:0,他引:62
C L Yeager R A Ashmun R K Williams C B Cardellichio L H Shapiro A T Look K V Holmes 《Nature》1992,357(6377):420-422
Human coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections. Here we report that human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells, is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human aminopeptidase N. By contrast, infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E infection, suggesting that the virus-binding site may lie at or near the active site of the human aminopeptidase molecule. 相似文献