全文获取类型
收费全文 | 16867篇 |
免费 | 39篇 |
国内免费 | 75篇 |
专业分类
系统科学 | 53篇 |
丛书文集 | 173篇 |
教育与普及 | 67篇 |
理论与方法论 | 49篇 |
现状及发展 | 7642篇 |
研究方法 | 659篇 |
综合类 | 8180篇 |
自然研究 | 158篇 |
出版年
2012年 | 196篇 |
2011年 | 334篇 |
2009年 | 99篇 |
2008年 | 261篇 |
2007年 | 287篇 |
2006年 | 264篇 |
2005年 | 281篇 |
2004年 | 323篇 |
2003年 | 288篇 |
2002年 | 280篇 |
2001年 | 466篇 |
2000年 | 491篇 |
1999年 | 337篇 |
1994年 | 304篇 |
1992年 | 268篇 |
1991年 | 223篇 |
1990年 | 278篇 |
1989年 | 252篇 |
1988年 | 260篇 |
1987年 | 282篇 |
1986年 | 290篇 |
1985年 | 338篇 |
1984年 | 233篇 |
1983年 | 257篇 |
1982年 | 212篇 |
1981年 | 204篇 |
1980年 | 245篇 |
1979年 | 508篇 |
1978年 | 434篇 |
1977年 | 390篇 |
1976年 | 314篇 |
1975年 | 386篇 |
1974年 | 474篇 |
1973年 | 422篇 |
1972年 | 431篇 |
1971年 | 562篇 |
1970年 | 608篇 |
1969年 | 531篇 |
1968年 | 532篇 |
1967年 | 459篇 |
1966年 | 408篇 |
1965年 | 294篇 |
1964年 | 128篇 |
1959年 | 166篇 |
1958年 | 322篇 |
1957年 | 253篇 |
1956年 | 202篇 |
1955年 | 200篇 |
1954年 | 193篇 |
1948年 | 167篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
981.
Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing 总被引:26,自引:0,他引:26
Yu G Nishimura M Arawaka S Levitan D Zhang L Tandon A Song YQ Rogaeva E Chen F Kawarai T Supala A Levesque L Yu H Yang DS Holmes E Milman P Liang Y Zhang DM Xu DH Sato C Rogaev E Smith M Janus C Zhang Y Aebersold R Farrer LS Sorbi S Bruni A Fraser P St George-Hyslop P 《Nature》2000,407(6800):48-54
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to those induced by simultaneous null mutations in both presenilin homologues of C. elegans (sel-12 and hop-1). Nicastrin also binds carboxy-terminal derivatives of beta-amyloid precursor protein (betaAPP), and modulates the production of the amyloid beta-peptide (A beta) from these derivatives. Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion. Deletions in this domain inhibit A beta production. Nicastrin and presenilins are therefore likely to be functional components of a multimeric complex necessary for the intramembranous proteolysis of proteins such as Notch/GLP-1 and betaAPP. 相似文献
982.
Zebra mussels (Dreissena polymorpha) are widespread and abundant in major freshwater ecosystems in North America, even though the phytoplankton food resources in some of these systems seem to be too low to sustain them. Because phytoplankton biomass is greatly depleted in ecosystems with large D. polymorpha populations and bacteria do not seem to be an important food source for this species, exploitation of alternative carbon sources may explain the unexpected success of D. polymorpha in such environments. Here we examine the possibility that absorption of dissolved organic carbon (DOC) from water could provide a nutritional supplement to zebra mussels. We find that mussels absorb 14C-labelled DOC produced by cultured diatoms with an efficiency of 0.23%; this indicates that DOC in natural waters could contribute up to 50% of the carbon demand of zebra mussels. We also find that zebra mussels absorb some dissolved metals that have been complexed by the DOM; although absorption of dissolved selenium was unaffected by DOC, absorption of dissolved cadmium, silver and mercury by the mussels increased 32-, 8.7- and 3.6-fold, respectively, in the presence of high-molecular-weight DOC. 相似文献
983.
A major enigma in evolutionary biology is that new forms or functions often require the concerted effects of several independent genetic changes. It is unclear how such changes might accumulate when they are likely to be deleterious individually and be lost by selective pressure. The Saccharomyces cerevisiae prion [PSI+] is an epigenetic modifier of the fidelity of translation termination, but its impact on yeast biology has been unclear. Here we show that [PSI+] provides the means to uncover hidden genetic variation and produce new heritable phenotypes. Moreover, in each of the seven genetic backgrounds tested, the constellation of phenotypes produced was unique. We propose that the epigenetic and metastable nature of [PSI+] inheritance allows yeast cells to exploit pre-existing genetic variation to thrive in fluctuating environments. Further, the capacity of [PSI+] to convert previously neutral genetic variation to a non-neutral state may facilitate the evolution of new traits. 相似文献
984.
The dry valleys of Antarctica are some of the oldest terrestrial surfaces on the Earth. Despite much study of soil weathering and development, ecosystem dynamics and the occurrence of life in these extreme environments, the reasons behind the exceptionally high salt content of the dry-valley soils have remained uncertain. In particular, the origins of sulphate are still controversial; proposed sources include wind-blown sea salt, chemical weatherings, marine incursion, hydrothermal processes and oxidation of biogenic sulphur in the atmosphere. Here we report measurements of delta18O and delta17O values of sulphates from a range of dry-valley soils. These sulphates all have a large positive anomaly of 17O, of up to 3.4/1000. This suggests that Antarctic sulphate comes not just from sea salt (which has no anomaly of 17O) but also from the atmospheric oxidation of reduced gaseous sulphur compounds, the only known process that can generate the observed 17O anomaly. This source is more prominent in high inland soils, suggesting that the distributions of sulphate are largely explained by differences in particle size and transport mode which exist between sea-salt aerosols and aerosols formed from biogenic sulphur emission. 相似文献
985.
DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure at 2.2 A of MutS from Escherichia coli bound to a G x T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutS alpha (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure. 相似文献
986.
Caffeine synthase gene from tea leaves 总被引:22,自引:0,他引:22
987.
The role of microbes in accretion, lamination and early lithification of modern marine stromatolites 总被引:28,自引:0,他引:28
Reid RP Visscher PT Decho AW Stolz JF Bebout BM Dupraz C Macintyre IG Paerl HW Pinckney JL Prufert-Bebout L Steppe TF DesMarais DJ 《Nature》2000,406(6799):989-992
For three billion years, before the Cambrian diversification of life, laminated carbonate build-ups called stromatolites were widespread in shallow marine seas. These ancient structures are generally thought to be microbial in origin and potentially preserve evidence of the Earth's earliest biosphere. Despite their evolutionary significance, little is known about stromatolite formation, especially the relative roles of microbial and environmental factors in stromatolite accretion. Here we show that growth of modern marine stromatolites represents a dynamic balance between sedimentation and intermittent lithification of cyanobacterial mats. Periods of rapid sediment accretion, during which stromatolite surfaces are dominated by pioneer communities of gliding filamentous cyanobacteria, alternate with hiatal intervals. These discontinuities in sedimentation are characterized by development of surface films of exopolymer and subsequent heterotrophic bacterial decomposition, forming thin crusts of microcrystalline carbonate. During prolonged hiatal periods, climax communities develop, which include endolithic coccoid cyanobacteria. These coccoids modify the sediment, forming thicker lithified laminae. Preservation of lithified layers at depth creates millimetre-scale lamination. This simple model of modern marine stromatolite growth may be applicable to ancient stromatolites. 相似文献
988.
989.
A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease 总被引:50,自引:0,他引:50
Janus C Pearson J McLaurin J Mathews PM Jiang Y Schmidt SD Chishti MA Horne P Heslin D French J Mount HT Nixon RA Mercken M Bergeron C Fraser PE St George-Hyslop P Westaway D 《Nature》2000,408(6815):979-982
Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species. 相似文献
990.
Fibroblast growth factor (FGF) signalling has been implicated in patterning, proliferation and cell differentiation in many organs, including the developing pancreas. Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands FGF1, FGF2, FGF4, FGF5, FGF7 and FGF10, are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. When we perturbed signalling by expressing dominant-negative forms of the receptors, FGFR1c and FGFR2b, in the pancreas, we found that that mice with attenuated FGFR1c signalling, but not those with reduced FGFR2b signalling, develop diabetes with age and exhibit a decreased number of beta-cells, impaired expression of glucose transporter 2 and increased proinsulin content in beta-cells owing to impaired expression of prohormone convertases 1/3 and 2. These defects are all characteristic of patients with type-2 diabetes. Mutations in the homeobox gene Ipf1/Pdx1 are linked to diabetes in both mouse and human. We also show that Ipf1/Pdx1 is required for the expression of FGFR1 signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of FGFR1 signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis. 相似文献