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排序方式: 共有348条查询结果,搜索用时 46 毫秒
341.
342.
Chen B Bronson RT Klaman LD Hampton TG Wang JF Green PJ Magnuson T Douglas PS Morgan JP Neel BG 《Nature genetics》2000,24(3):296-299
Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease. 相似文献
343.
de Bernardis P Ade PA Bock JJ Bond JR Borrill J Boscaleri A Coble K Crill BP De Gasperis G Farese PC Ferreira PG Ganga K Giacometti M Hivon E Hristov VV Iacoangeli A Jaffe AH Lange AE Martinis L Masi S Mason PV Mauskopf PD Melchiorri A Miglio L Montroy T Netterfield CB 《Nature》2000,404(6781):955-959
The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73 K cosmic microwave background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the Universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole Ipeak = (197 +/- 6), with an amplitude delta T200 = (69 +/- 8) microK. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary models. 相似文献
344.
Digital selection and analogue amplification coexist in a cortex-inspired silicon circuit 总被引:2,自引:0,他引:2
Digital circuits such as the flip-flop use feedback to achieve multistability and nonlinearity to restore signals to logical levels, for example 0 and 1. Analogue feedback circuits are generally designed to operate linearly, so that signals are over a range, and the response is unique. By contrast, the response of cortical circuits to sensory stimulation can be both multistable and graded. We propose that the neocortex combines digital selection of an active set of neurons with analogue response by dynamically varying the positive feedback inherent in its recurrent connections. Strong positive feedback causes differential instabilities that drive the selection of a set of active neurons under the constraints embedded in the synaptic weights. Once selected, the active neurons generate weaker, stable feedback that provides analogue amplification of the input. Here we present our model of cortical processing as an electronic circuit that emulates this hybrid operation, and so is able to perform computations that are similar to stimulus selection, gain modulation and spatiotemporal pattern generation in the neocortex. 相似文献
345.
Nanog safeguards pluripotency and mediates germline development 总被引:3,自引:0,他引:3
Chambers I Silva J Colby D Nichols J Nijmeijer B Robertson M Vrana J Jones K Grotewold L Smith A 《Nature》2007,450(7173):1230-1234
346.
347.
Seandel M James D Shmelkov SV Falciatori I Kim J Chavala S Scherr DS Zhang F Torres R Gale NW Yancopoulos GD Murphy A Valenzuela DM Hobbs RM Pandolfi PP Rafii S 《Nature》2007,449(7160):346-350
Adult mammalian testis is a source of pluripotent stem cells. However, the lack of specific surface markers has hampered identification and tracking of the unrecognized subset of germ cells that gives rise to multipotent cells. Although embryonic-like cells can be derived from adult testis cultures after only several weeks in vitro, it is not known whether adult self-renewing spermatogonia in long-term culture can generate such stem cells as well. Here, we show that highly proliferative adult spermatogonial progenitor cells (SPCs) can be efficiently obtained by cultivation on mitotically inactivated testicular feeders containing CD34+ stromal cells. SPCs exhibit testicular repopulating activity in vivo and maintain the ability in long-term culture to give rise to multipotent adult spermatogonial-derived stem cells (MASCs). Furthermore, both SPCs and MASCs express GPR125, an orphan adhesion-type G-protein-coupled receptor. In knock-in mice bearing a GPR125-beta-galactosidase (LacZ) fusion protein under control of the native Gpr125 promoter (GPR125-LacZ), expression in the testis was detected exclusively in spermatogonia and not in differentiated germ cells. Primary GPR125-LacZ SPC lines retained GPR125 expression, underwent clonal expansion, maintained the phenotype of germline stem cells, and reconstituted spermatogenesis in busulphan-treated mice. Long-term cultures of GPR125+ SPCs (GSPCs) also converted into GPR125+ MASC colonies. GPR125+ MASCs generated derivatives of the three germ layers and contributed to chimaeric embryos, with concomitant downregulation of GPR125 during differentiation into GPR125- cells. MASCs also differentiated into contractile cardiac tissue in vitro and formed functional blood vessels in vivo. Molecular bookmarking by GPR125 in the adult mouse and, ultimately, in the human testis could enrich for a population of SPCs for derivation of GPR125+ MASCs, which may be employed for genetic manipulation, tissue regeneration and revascularization of ischaemic organs. 相似文献
348.
Easton DF Pooley KA Dunning AM Pharoah PD Thompson D Ballinger DG Struewing JP Morrison J Field H Luben R Wareham N Ahmed S Healey CS Bowman R;SEARCH collaborators Meyer KB Haiman CA Kolonel LK Henderson BE Le Marchand L Brennan P Sangrajrang S Gaborieau V Odefrey F Shen CY Wu PE Wang HC Eccles D Evans DG Peto J Fletcher O Johnson N Seal S Stratton MR Rahman N Chenevix-Trench G Bojesen SE Nordestgaard BG Axelsson CK Garcia-Closas M Brinton L Chanock S Lissowska J Peplonska B Nevanlinna H 《Nature》2007,447(7148):1087-1093
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. 相似文献