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451.
Gustavo E. Romero Daniela Pérez Federico G. López Armengol 《Foundations of Science》2018,23(2):415-426
Macroscopic irreversible processes emerge from fundamental physical laws of reversible character. The source of the local irreversibility seems to be not in the laws themselves but in the initial and boundary conditions of the equations that represent the laws. In this work we propose that the screening of currents by black hole event horizons determines, locally, a preferred direction for the flux of electromagnetic energy. We study the growth of black hole event horizons due to the cosmological expansion and accretion of cosmic microwave background radiation, for different cosmological models. We propose generalized McVittie co-moving metrics and integrate the rate of accretion of cosmic microwave background radiation onto a supermassive black hole over cosmic time. We find that for flat, open, and closed Friedmann cosmological models, the ratio of the total area of the black hole event horizons with respect to the area of a radial co-moving space-like hypersurface always increases. Since accretion of cosmic radiation sets an absolute lower limit to the total matter accreted by black holes, this implies that the causal past and future are not mirror symmetric for any spacetime event. The asymmetry causes a net Poynting flux in the global future direction; the latter is in turn related to the ever increasing thermodynamic entropy. Thus, we expose a connection between four different “time arrows”: cosmological, electromagnetic, gravitational, and thermodynamic. 相似文献
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455.
Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315
456.
Stacey SN Sulem P Jonasdottir A Masson G Gudmundsson J Gudbjartsson DF Magnusson OT Gudjonsson SA Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Nexø BA Tjønneland A Overvad K Rudnai P Gurzau E Koppova K Hemminki K Corredera C Fuentelsaz V Grasa P Navarrete S Fuertes F García-Prats MD Sanambrosio E Panadero A De Juan A Garcia A Rivera F Planelles D Soriano V Requena C Aben KK van Rossum MM Cremers RG van Oort IM van Spronsen DJ Schalken JA Peters WH Helfand BT Donovan JL 《Nature genetics》2011,43(11):1098-1103
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27). 相似文献
457.
Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
458.
Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia 总被引:1,自引:0,他引:1
Zenatti PP Ribeiro D Li W Zuurbier L Silva MC Paganin M Tritapoe J Hixon JA Silveira AB Cardoso BA Sarmento LM Correia N Toribio ML Kobarg J Horstmann M Pieters R Brandalise SR Ferrando AA Meijerink JP Durum SK Yunes JA Barata JT 《Nature genetics》2011,43(10):932-939
Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL. 相似文献
459.
Yang J Manolio TA Pasquale LR Boerwinkle E Caporaso N Cunningham JM de Andrade M Feenstra B Feingold E Hayes MG Hill WG Landi MT Alonso A Lettre G Lin P Ling H Lowe W Mathias RA Melbye M Pugh E Cornelis MC Weir BS Goddard ME Visscher PM 《Nature genetics》2011,43(6):519-525
We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ~0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. 相似文献
460.
Putoux A Thomas S Coene KL Davis EE Alanay Y Ogur G Uz E Buzas D Gomes C Patrier S Bennett CL Elkhartoufi N Frison MH Rigonnot L Joyé N Pruvost S Utine GE Boduroglu K Nitschke P Fertitta L Thauvin-Robinet C Munnich A Cormier-Daire V Hennekam R Colin E Akarsu NA Bole-Feysot C Cagnard N Schmitt A Goudin N Lyonnet S Encha-Razavi F Siffroi JP Winey M Katsanis N Gonzales M Vekemans M Beales PL Attié-Bitach T 《Nature genetics》2011,43(6):601-606