全文获取类型
收费全文 | 31351篇 |
免费 | 48篇 |
国内免费 | 68篇 |
专业分类
系统科学 | 154篇 |
丛书文集 | 717篇 |
教育与普及 | 79篇 |
理论与方法论 | 200篇 |
现状及发展 | 13501篇 |
研究方法 | 1347篇 |
综合类 | 15100篇 |
自然研究 | 369篇 |
出版年
2013年 | 174篇 |
2012年 | 419篇 |
2011年 | 832篇 |
2010年 | 180篇 |
2008年 | 552篇 |
2007年 | 539篇 |
2006年 | 596篇 |
2005年 | 591篇 |
2004年 | 517篇 |
2003年 | 567篇 |
2002年 | 566篇 |
2001年 | 978篇 |
2000年 | 896篇 |
1999年 | 598篇 |
1992年 | 569篇 |
1991年 | 462篇 |
1990年 | 486篇 |
1989年 | 489篇 |
1988年 | 490篇 |
1987年 | 498篇 |
1986年 | 490篇 |
1985年 | 599篇 |
1984年 | 494篇 |
1983年 | 404篇 |
1982年 | 346篇 |
1981年 | 340篇 |
1980年 | 448篇 |
1979年 | 967篇 |
1978年 | 855篇 |
1977年 | 846篇 |
1976年 | 580篇 |
1975年 | 630篇 |
1974年 | 931篇 |
1973年 | 785篇 |
1972年 | 804篇 |
1971年 | 1017篇 |
1970年 | 1339篇 |
1969年 | 1004篇 |
1968年 | 945篇 |
1967年 | 988篇 |
1966年 | 829篇 |
1965年 | 609篇 |
1964年 | 148篇 |
1959年 | 360篇 |
1958年 | 522篇 |
1957年 | 443篇 |
1956年 | 366篇 |
1955年 | 316篇 |
1954年 | 363篇 |
1948年 | 193篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
311.
Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells 总被引:102,自引:0,他引:102
R L Williams D J Hilton S Pease T A Willson C L Stewart D P Gearing E F Wagner D Metcalf N A Nicola N M Gough 《Nature》1988,336(6200):684-687
Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice. 相似文献
312.
A universal marker for transgenic insects 总被引:16,自引:0,他引:16
313.
Stem cells, cancer, and cancer stem cells. 总被引:312,自引:0,他引:312
Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis. 相似文献
314.
Is there a decline in marine phytoplankton? 总被引:1,自引:0,他引:1
McQuatters-Gollop A Reid PC Edwards M Burkill PH Castellani C Batten S Gieskes W Beare D Bidigare RR Head E Johnson R Kahru M Koslow JA Pena A 《Nature》2011,472(7342):E6-7; discussion E8-9
315.
The p53 tumour suppressor gene 总被引:266,自引:0,他引:266
The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers. 相似文献
316.
317.
HIV preferentially infects HIV-specific CD4+ T cells 总被引:34,自引:0,他引:34
Douek DC Brenchley JM Betts MR Ambrozak DR Hill BJ Okamoto Y Casazza JP Kuruppu J Kunstman K Wolinsky S Grossman Z Dybul M Oxenius A Price DA Connors M Koup RA 《Nature》2002,417(6884):95-98
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption. 相似文献
318.
Angiotensin-converting enzyme 2 is an essential regulator of heart function 总被引:131,自引:0,他引:131
Crackower MA Sarao R Oudit GY Yagil C Kozieradzki I Scanga SE Oliveira-dos-Santos AJ da Costa J Zhang L Pei Y Scholey J Ferrario CM Manoukian AS Chappell MC Backx PH Yagil Y Penninger JM 《Nature》2002,417(6891):822-828
Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo. 相似文献
319.
Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels 总被引:5,自引:0,他引:5
Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting about 1 in 3,500 males. It is allelic with the milder Becker muscular dystrophy. The biochemical basis for both diseases is unknown and no effective treatment is available. Long-range physical mapping has shown that the DMD gene, localized in Xp21, is extremely large, exceeding 2 million base pairs. Until now, carrier detection and prenatal diagnosis has involved the use of linked restriction fragment length polymorphism markers which detect muscular dystrophy-associated deletions in about 10% of the cases. Field inversion gel electrophoresis (FIGE) allows the detection of structural rearrangements in 21 out of 39 of the DMD patients studied (54%), of which 14 (65%) were not detected by conventional methods. Large deletions seem to make up a much higher fraction of the DMD mutations than so far indicated by other methods. A region prone to deletion was located in the distal half of the gene. FIGE analysis could provide a valuable extension of information for carrier detection and prenatal diagnosis. The technique should be generally applicable to the study of diseases involving structural chromosomal rearrangements. 相似文献
320.
The genome sequence of the rice blast fungus Magnaporthe grisea 总被引:8,自引:0,他引:8
Dean RA Talbot NJ Ebbole DJ Farman ML Mitchell TK Orbach MJ Thon M Kulkarni R Xu JR Pan H Read ND Lee YH Carbone I Brown D Oh YY Donofrio N Jeong JS Soanes DM Djonovic S Kolomiets E Rehmeyer C Li W Harding M Kim S Lebrun MH Bohnert H Coughlan S Butler J Calvo S Ma LJ Nicol R Purcell S Nusbaum C Galagan JE Birren BW 《Nature》2005,434(7036):980-986
Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation. 相似文献