全文获取类型
收费全文 | 1388篇 |
免费 | 4篇 |
国内免费 | 14篇 |
专业分类
系统科学 | 108篇 |
丛书文集 | 2篇 |
教育与普及 | 10篇 |
理论与方法论 | 27篇 |
现状及发展 | 203篇 |
研究方法 | 191篇 |
综合类 | 753篇 |
自然研究 | 112篇 |
出版年
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 12篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 34篇 |
2012年 | 106篇 |
2011年 | 224篇 |
2010年 | 37篇 |
2009年 | 7篇 |
2008年 | 95篇 |
2007年 | 96篇 |
2006年 | 85篇 |
2005年 | 120篇 |
2004年 | 109篇 |
2003年 | 100篇 |
2002年 | 93篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 14篇 |
1993年 | 5篇 |
1992年 | 19篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 5篇 |
1972年 | 3篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1958年 | 2篇 |
1957年 | 4篇 |
1956年 | 2篇 |
排序方式: 共有1406条查询结果,搜索用时 15 毫秒
761.
McGregor L Makela V Darling SM Vrontou S Chalepakis G Roberts C Smart N Rutland P Prescott N Hopkins J Bentley E Shaw A Roberts E Mueller R Jadeja S Philip N Nelson J Francannet C Perez-Aytes A Megarbane A Kerr B Wainwright B Woolf AS Winter RM Scambler PJ 《Nature genetics》2003,34(2):203-208
Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero. 相似文献
762.
Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency 总被引:22,自引:0,他引:22
763.
A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans 总被引:9,自引:0,他引:9
Crittenden SL Bernstein DS Bachorik JL Thompson BE Gallegos M Petcherski AG Moulder G Barstead R Wickens M Kimble J 《Nature》2002,417(6889):660-663
Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes. The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell. FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF ('fem-3 mRNA binding factor'), were originally discovered as regulators of germline sex determination. Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle. FBF belongs to the PUF family ('Pumilio and FBF') of RNA-binding proteins. Pumilio controls germline stem cells in Drosophila females, and, in lower eukaryotes, PUF proteins promote continued mitoses. We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells. 相似文献
764.
765.
The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair 总被引:17,自引:0,他引:17
Hopfner KP Craig L Moncalian G Zinkel RA Usui T Owen BA Karcher A Henderson B Bodmer JL McMurray CT Carney JP Petrini JH Tainer JA 《Nature》2002,418(6897):562-566
The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. These functions all imply that the linked binding of two DNA substrates occurs, although the molecular basis for this process remains unknown. Here we present a 2.2 A crystal structure of the Rad50 coiled-coil region that reveals an unexpected dimer interface at the apex of the coiled coils in which pairs of conserved Cys-X-X-Cys motifs form interlocking hooks that bind one Zn(2+) ion. Biochemical, X-ray and electron microscopy data indicate that these hooks can join oppositely protruding Rad50 coiled-coil domains to form a flexible bridge of up to 1,200 A. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain. The Rad50 hook is functional, because mutations in this motif confer radiation sensitivity in yeast and disrupt binding at the distant Mre11 nuclease interface. These data support an architectural role for the Rad50 coiled coils in forming metal-mediated bridging complexes between two DNA-binding heads. The resulting assemblies have appropriate lengths and conformational properties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining. 相似文献
766.
767.
Microsporidia are obligate intracellular parasites of several eukaryotes. They have a highly complex and unique infection apparatus but otherwise appear structurally simple. Microsporidia are thought to lack typical eukaryotic organelles, such as mitochondria and peroxisomes. This has been interpreted as support for the hypothesis that these peculiar eukaryotes diverged before the mitochondrial endosymbiosis, which would make them one of the earliest offshoots in eukaryotic evolution. But microsporidial nuclear genes that encode orthologues of typical mitochondrial heatshock Hsp70 proteins have been detected, which provides evidence for secondary loss of the organelle or endosymbiont. In addition, gene trees and more sophisticated phylogenetic analyses have recovered microsporidia as the relatives of fungi, rather than as basal eukaryotes. Here we show that a highly specific antibody raised against a Trachipleistophora hominis Hsp70 protein detects the presence, under light and electron microscopy, of numerous tiny ( approximately 50 x 90 nm) organelles with double membranes in this human microsporidial parasite. The finding of relictual mitochondria in microsporidia provides further evidence of the reluctance of eukaryotes to lose the mitochondrial organelle, even when its canonical function of aerobic respiration has been apparently lost. 相似文献
768.
Magnetic anomalies associated with slowly cooled igneous and metamorphic rocks are commonly attributed to the presence of the mineral magnetite. Although the intermediate members of the ilmenite-haematite mineral series can also carry a strong ferrimagnetic remanence, it is preserved only in rapidly cooled volcanic rocks, where formation of intergrowths of weakly magnetic haematite and paramagnetic ilmenite is suppressed. But the occurrence of unusually large and stable magnetic remanence in rocks containing such intergrowths has been known for decades, and has recently been the subject of intense investigation. These unmixed oxide phases have been shown to contain pervasive exsolution lamellae with thickness from 100 microm down to about 1 nm (one unit cell). These rocks, many of which contain only a few per cent of such oxides, show natural remanent magnetizations up to 30 A m(-1) --too strong to be explained even by pure haematite in an unsaturated state. Here we propose a new ferrimagnetic substructure created by ferrous-ferric 'contact layers' that reduce charge imbalance along lamellar contacts between antiferromagnetic haematite and paramagnetic ilmenite. We estimate that such a lamellar magnetic material can have a saturation magnetization up to 55 kA m(-1) --22 times stronger than pure haematite-- while retaining the high coercivity and thermal properties of single-domain haematite. 相似文献
769.
Methylating agents generate cytotoxic and mutagenic DNA damage. Cells use 3-methyladenine-DNA glycosylases to excise some methylated bases from DNA, and suicidal O(6)-methylguanine-DNA methyltransferases to transfer alkyl groups from other lesions onto a cysteine residue. Here we report that the highly conserved AlkB protein repairs DNA alkylation damage by means of an unprecedented mechanism. AlkB has no detectable nuclease, DNA glycosylase or methyltransferase activity; however, Escherichia coli alkB mutants are defective in processing methylation damage generated in single-stranded DNA. Theoretical protein fold recognition had suggested that AlkB resembles the Fe(ii)- and alpha-ketoglutarate-dependent dioxygenases, which use iron-oxo intermediates to oxidize chemically inert compounds. We show here that purified AlkB repairs the cytotoxic lesions 1-methyladenine and 3-methylcytosine in single- and double-stranded DNA in a reaction that is dependent on oxygen, alpha-ketoglutarate and Fe(ii). The AlkB enzyme couples oxidative decarboxylation of alpha-ketoglutarate to the hydroxylation of these methylated bases in DNA, resulting in direct reversion to the unmodified base and the release of formaldehyde. 相似文献
770.
Irigoien X Harris RP Verheye HM Joly P Runge J Starr M Pond D Campbell R Shreeve R Ward P Smith AN Dam HG Peterson W Tirelli V Koski M Smith T Harbour D Davidson R 《Nature》2002,419(6905):387-389
Diatoms dominate spring bloom phytoplankton assemblages in temperate waters and coastal upwelling regions of the global ocean. Copepods usually dominate the zooplankton in these regions and are the prey of many larval fish species. Recent laboratory studies suggest that diatoms may have a deleterious effect on the success of copepod egg hatching. These findings challenge the classical view of marine food-web energy flow from diatoms to fish by means of copepods. Egg mortality is an important factor in copepod population dynamics, thus, if diatoms have a deleterious in situ effect, paradoxically, high diatom abundance could limit secondary production. Therefore, the current understanding of energy transfer from primary production to fisheries in some of the most productive and economically important marine ecosystems may be seriously flawed. Here we present in situ estimates of copepod egg hatching success from twelve globally distributed areas, where diatoms dominate the phytoplankton assemblage. We did not observe a negative relationship between copepod egg hatching success and either diatom biomass or dominance in the microplankton in any of these regions. The classical model for diatom-dominated system remains valid. 相似文献