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991.
Baudrand R Campino C Carvajal CA Olivieri O Guidi G Faccini G Sateler J Cornejo J Martin BS Dominguez JM Cerda J Mosso LM Owen GI Kalergis AM Fardella CE 《Steroids》2011,76(14):1575-1581
Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24 h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p < 0.001), waist circumference (r = +0.38, p < 0.01), glycemia (r = +0.37, p < 0.01), and triglycerides (r = +0.18, p = 0.06) and negatively correlated with adiponectin (r = −0.36, p < 0.001), HOMA-β (r = −0.21, p < 0.001) and HDL (r = −0.29, p < 0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing’s syndrome. 相似文献
992.
Ruzov A Tsenkina Y Serio A Dudnakova T Fletcher J Bai Y Chebotareva T Pells S Hannoun Z Sullivan G Chandran S Hay DC Bradley M Wilmut I De Sousa P 《Cell research》2011,21(9):1332-1342
Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cellular systems, and show that the developmental dynamics of 5-hmC are different from those of 5-methylcytosine (5-mC); in particular 5-hmC is enriched in embryonic contexts compared to adult tissues. A detectable 5-hmC signal appears in pre-implantation development starting at the zygote stage, where the paternal genome is subjected to a genome-wide hydroxylation of 5-mC, which precisely coincides with the loss of the 5-mC signal in the paternal pronucleus. Levels of 5-hmC are high in cells of the inner cell mass in blastocysts, and the modification colocalises with nestin-expressing cell populations in mouse post-implantation embryos. Compared to other adult mammalian organs, 5-hmC is strongly enriched in bone marrow and brain, wherein high 5-hmC content is a feature of both neuronal progenitors and post-mitotic neurons. We show that high levels of 5-hmC are not only present in mouse and human embryonic stem cells (ESCs) and lost during differentiation, as has been reported previously, but also reappear during the generation of induced pluripotent stem cells; thus 5-hmC enrichment correlates with a pluripotent cell state. Our findings suggest that apart from the cells of neuronal lineages, high levels of genomic 5-hmC are an epigenetic feature of embryonic cell populations and cellular pluri- and multi-lineage potency. To our knowledge, 5-hmC represents the first epigenetic modification of DNA discovered whose enrichment is so cell-type specific. 相似文献
993.
994.
Emanuele Kuhn Andrew S. Ichimura Vivian Peng Christian H. Fritsen Gareth Trubl Peter T. Doran Alison E. Murray 《Applied and environmental microbiology》2014,80(12):3687-3698
The anoxic and freezing brine that permeates Lake Vida''s perennial ice below 16 m contains an abundance of very small (≤0.2-μm) particles mixed with a less abundant population of microbial cells ranging from >0.2 to 1.5 μm in length. Fluorescent DNA staining, electron microscopy (EM) observations, elemental analysis, and extraction of high-molecular-weight genomic DNA indicated that a significant portion of these ultrasmall particles are cells. A continuous electron-dense layer surrounding a less electron-dense region was observed by EM, indicating the presence of a biological membrane surrounding a cytoplasm. The ultrasmall cells are 0.192 ± 0.065 μm, with morphology characteristic of coccoid and diplococcic bacterial cells, often surrounded by iron-rich capsular structures. EM observations also detected the presence of smaller unidentified nanoparticles of 0.020 to 0.140 μm among the brine cells. A 16S rRNA gene clone library from the brine 0.1- to 0.2-μm-size fraction revealed a relatively low-diversity assemblage of Bacteria sequences distinct from the previously reported >0.2-μm-cell-size Lake Vida brine assemblage. The brine 0.1- to 0.2-μm-size fraction was dominated by the Proteobacteria-affiliated genera Herbaspirillum, Pseudoalteromonas, and Marinobacter. Cultivation efforts of the 0.1- to 0.2-μm-size fraction led to the isolation of Actinobacteria-affiliated genera Microbacterium and Kocuria. Based on phylogenetic relatedness and microscopic observations, we hypothesize that the ultrasmall cells in Lake Vida brine are ultramicrocells that are likely in a reduced size state as a result of environmental stress or life cycle-related conditions. 相似文献
995.
Weixing Zhao Dorina Saro Michal Hammel YoungHo Kwon Yuanyuan Xu Robert P. Rambo Gareth J. Williams Peter Chi Lucy Lu Roberto J. Pezza R. Daniel Camerini-Otero John A. Tainer Hong-Wei Wang Patrick Sung 《Nucleic acids research》2014,42(2):906-917
The Hop2–Mnd1 complex functions with the DMC1 recombinase in meiotic recombination. Hop2–Mnd1 stabilizes the DMC1-single-stranded DNA (ssDNA) filament and promotes the capture of the double-stranded DNA partner by the recombinase filament to assemble the synaptic complex. Herein, we define the action mechanism of Hop2–Mnd1 in DMC1-mediated recombination. Small angle X-ray scattering analysis and electron microscopy reveal that the heterodimeric Hop2–Mnd1 is a V-shaped molecule. We show that the protein complex harbors three distinct DNA binding sites, and determine their functional relevance. Specifically, the N-terminal double-stranded DNA binding functions of Hop2 and Mnd1 co-operate to mediate synaptic complex assembly, whereas ssDNA binding by the Hop2 C-terminus helps stabilize the DMC1-ssDNA filament. A model of the Hop2-Mnd1-DMC1-ssDNA ensemble is proposed to explain how it mediates homologous DNA pairing in meiotic recombination. 相似文献
996.
Marcelo R. de Carvalho Malte C. Ebach David M. Williams Silvio S. Nihei Miguel Trefaut Rodrigues Taran Grant Luís F. Silveira Hussam Zaher Anthony C. Gill Robert C. Schelly John S. Sparks Flávio A. Bockmann Bernard Séret Hsuan‐Ching Ho Lance Grande Olivier Rieppel Alain Dubois Annemarie Ohler Julián Faivovich Leandro C. S. Assis Quentin D. Wheeler Paul Z. Goldstein Eduardo A. B. de Almeida Antonio G. Valdecasas Gareth Nelson 《Cladistics : the international journal of the Willi Hennig Society》2014,30(3):322-329
997.
Erin W. Dickie Amir Tahmasebi Leon French Natasa Kovacevic Tobias Banaschewski Gareth J. Barker Arun Bokde Christian Büchel Patricia Conrod Herta Flor Hugh Garavan Juergen Gallinat Penny Gowland Andreas Heinz Bernd Ittermann Claire Lawrence Karl Mann Jean-Luc Martinot Frauke Nees Thomas Nichols Mark Lathrop Eva Loth Zdenka Pausova Marcela Rietschel Michal N. Smolka Andreas Str?hle Roberto Toro Gunter Schumann the IMAGEN consortium Tomá? Paus 《PLoS genetics》2014,10(8)
Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. 相似文献
998.
Gareth Hagger-Johnson Ian J. Deary Carolyn A. Davies Alexander Weiss G. David Batty 《PloS one》2014,9(1)
Objective
Studies examining the relation of information processing speed, as measured by reaction time, with mortality are scarce. We explored these associations in a representative sample of the US population.Methods
Participants were 5,134 adults (2,342 men) aged 20–59 years from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94).Results
Adjusted for age, sex, and ethnic minority status, a 1 SD slower reaction time was associated with a raised risk of mortality from all-causes (HR = 1.25, 95% CI 1.12, 1.39) and cardiovascular disease (CVD) (HR = 1.36, 95% CI 1.17, 1.58). Having 1 SD more variable reaction time was also associated with greater risk of all-cause (HR = 1.36, 95% CI 1.19, 1.55) and CVD (HR = 1.50, 95% CI 1.33, 1.70) mortality. No associations were observed for cancer mortality. The magnitude of the relationships was comparable in size to established risk factors in this dataset, such as smoking.Interpretation
Alongside better-established risk factors, reaction time is associated with increased risk of premature death and cardiovascular disease. It is a candidate risk factor for all-cause and cause-specific mortality. 相似文献999.
Amanda Worker Camilla Blain Jozef Jarosz K. Ray Chaudhuri Gareth J. Barker Steven C. R. Williams Richard Brown P. Nigel Leigh Andrew Simmons 《PloS one》2014,9(12)
Objective
Parkinson''s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features.Methods
High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group.Results
Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology.Conclusion
These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients. 相似文献1000.
Antony M. Latham Jayakanth Kankanala Gareth W. Fearnley Matthew C. Gage Mark T. Kearney Shervanthi Homer-Vanniasinkam Stephen B. Wheatcroft Colin W. G. Fishwick Sreenivasan Ponnambalam 《PloS one》2014,9(11)