全文获取类型
收费全文 | 12825篇 |
免费 | 215篇 |
国内免费 | 556篇 |
专业分类
系统科学 | 1453篇 |
丛书文集 | 473篇 |
教育与普及 | 1889篇 |
理论与方法论 | 129篇 |
现状及发展 | 715篇 |
研究方法 | 1047篇 |
综合类 | 7848篇 |
自然研究 | 42篇 |
出版年
2021年 | 37篇 |
2018年 | 46篇 |
2017年 | 64篇 |
2016年 | 63篇 |
2015年 | 72篇 |
2014年 | 147篇 |
2013年 | 87篇 |
2012年 | 553篇 |
2011年 | 718篇 |
2010年 | 244篇 |
2009年 | 81篇 |
2008年 | 616篇 |
2007年 | 738篇 |
2006年 | 889篇 |
2005年 | 1016篇 |
2004年 | 736篇 |
2003年 | 817篇 |
2002年 | 585篇 |
2001年 | 553篇 |
2000年 | 661篇 |
1999年 | 350篇 |
1998年 | 133篇 |
1997年 | 78篇 |
1996年 | 82篇 |
1995年 | 60篇 |
1994年 | 87篇 |
1993年 | 139篇 |
1992年 | 124篇 |
1991年 | 128篇 |
1990年 | 103篇 |
1989年 | 126篇 |
1988年 | 176篇 |
1987年 | 190篇 |
1986年 | 228篇 |
1985年 | 216篇 |
1984年 | 236篇 |
1983年 | 215篇 |
1982年 | 214篇 |
1981年 | 181篇 |
1980年 | 149篇 |
1979年 | 76篇 |
1964年 | 34篇 |
1959年 | 164篇 |
1958年 | 286篇 |
1957年 | 195篇 |
1956年 | 160篇 |
1955年 | 180篇 |
1954年 | 169篇 |
1948年 | 38篇 |
1946年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
361.
Konhauser KO Lalonde SV Planavsky NJ Pecoits E Lyons TW Mojzsis SJ Rouxel OJ Barley ME Rosìere C Fralick PW Kump LR Bekker A 《Nature》2011,478(7369):369-373
The enrichment of redox-sensitive trace metals in ancient marine sedimentary rocks has been used to determine the timing of the oxidation of the Earth's land surface. Chromium (Cr) is among the emerging proxies for tracking the effects of atmospheric oxygenation on continental weathering; this is because its supply to the oceans is dominated by terrestrial processes that can be recorded in the Cr isotope composition of Precambrian iron formations. However, the factors controlling past and present seawater Cr isotope composition are poorly understood. Here we provide an independent and complementary record of marine Cr supply, in the form of Cr concentrations and authigenic enrichment in iron-rich sedimentary rocks. Our data suggest that Cr was largely immobile on land until around 2.48?Gyr ago, but within the 160?Myr that followed--and synchronous with independent evidence for oxygenation associated with the Great Oxidation Event (see, for example, refs 4-6)--marked excursions in Cr content and Cr/Ti ratios indicate that Cr was solubilized at a scale unrivalled in history. As Cr isotope fractionations at that time were muted, Cr must have been mobilized predominantly in reduced, Cr(III), form. We demonstrate that only the oxidation of an abundant and previously stable crustal pyrite reservoir by aerobic-respiring, chemolithoautotrophic bacteria could have generated the degree of acidity required to solubilize Cr(III) from ultramafic source rocks and residual soils. This profound shift in weathering regimes beginning at 2.48?Gyr ago constitutes the earliest known geochemical evidence for acidophilic aerobes and the resulting acid rock drainage, and accounts for independent evidence of an increased supply of dissolved sulphate and sulphide-hosted trace elements to the oceans around that time. Our model adds to amassing evidence that the Archaean-Palaeoproterozoic boundary was marked by a substantial shift in terrestrial geochemistry and biology. 相似文献
362.
A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours 总被引:1,自引:0,他引:1
Beck B Driessens G Goossens S Youssef KK Kuchnio A Caauwe A Sotiropoulou PA Loges S Lapouge G Candi A Mascre G Drogat B Dekoninck S Haigh JJ Carmeliet P Blanpain C 《Nature》2011,478(7369):399-403
Angiogenesis is critical during tumour initiation and malignant progression. Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients. It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies. Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin. Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers. 相似文献
363.
364.
365.
Direct observations over the past four centuries show that the number of sunspots observed on the Sun's surface varies periodically, going through successive maxima and minima. Following sunspot cycle 23, the Sun went into a prolonged minimum characterized by a very weak polar magnetic field and an unusually large number of days without sunspots. Sunspots are strongly magnetized regions generated by a dynamo mechanism that recreates the solar polar field mediated through plasma flows. Here we report results from kinematic dynamo simulations which demonstrate that a fast meridional flow in the first half of a cycle, followed by a slower flow in the second half, reproduces both characteristics of the minimum of sunspot cycle 23. Our model predicts that, in general, very deep minima are associated with weak polar fields. Sunspots govern the solar radiative energy and radio flux, and, in conjunction with the polar field, modulate the solar wind, the heliospheric open flux and, consequently, the cosmic ray flux at Earth. 相似文献
366.
367.
Melt-induced speed-up of Greenland ice sheet offset by efficient subglacial drainage 总被引:1,自引:0,他引:1
Fluctuations in surface melting are known to affect the speed of glaciers and ice sheets, but their impact on the Greenland ice sheet in a warming climate remains uncertain. Although some studies suggest that greater melting produces greater ice-sheet acceleration, others have identified a long-term decrease in Greenland's flow despite increased melting. Here we use satellite observations of ice motion recorded in a land-terminating sector of southwest Greenland to investigate the manner in which ice flow develops during years of markedly different melting. Although peak rates of ice speed-up are positively correlated with the degree of melting, mean summer flow rates are not, because glacier slowdown occurs, on average, when a critical run-off threshold of about 1.4?centimetres a day is exceeded. In contrast to the first half of summer, when flow is similar in all years, speed-up during the latter half is 62?±?16 per cent less in warmer years. Consequently, in warmer years, the period of fast ice flow is three times shorter and, overall, summer ice flow is slower. This behaviour is at odds with that expected from basal lubrication alone. Instead, it mirrors that of mountain glaciers, where melt-induced acceleration of flow ceases during years of high melting once subglacial drainage becomes efficient. A model of ice-sheet flow that captures switching between cavity and channel drainage modes is consistent with the run-off threshold, fast-flow periods, and later-summer speeds we have observed. Simulations of the Greenland ice-sheet flow under climate warming scenarios should account for the dynamic evolution of subglacial drainage; a simple model of basal lubrication alone misses key aspects of the ice sheet's response to climate warming. 相似文献
368.
Suhre K Shin SY Petersen AK Mohney RP Meredith D Wägele B Altmaier E;CARDIoGRAM Deloukas P Erdmann J Grundberg E Hammond CJ de Angelis MH Kastenmüller G Köttgen A Kronenberg F Mangino M Meisinger C Meitinger T Mewes HW Milburn MV Prehn C Raffler J Ried JS Römisch-Margl W Samani NJ Small KS Wichmann HE Zhai G Illig T Spector TD Adamski J Soranzo N Gieger C 《Nature》2011,477(7362):54-60
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research. 相似文献
369.
Spatio-temporal transcriptome of the human brain 总被引:1,自引:0,他引:1
370.
Programming the magnitude and persistence of antibody responses with innate immunity 总被引:1,自引:0,他引:1
Kasturi SP Skountzou I Albrecht RA Koutsonanos D Hua T Nakaya HI Ravindran R Stewart S Alam M Kwissa M Villinger F Murthy N Steel J Jacob J Hogan RJ García-Sastre A Compans R Pulendran B 《Nature》2011,470(7335):543-547
Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques. 相似文献