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991.
Lessard CJ Adrianto I Kelly JA Kaufman KM Grundahl KM Adler A Williams AH Gallant CJ;Marta E. Alarcón-Riquelme on behalf of the BIOLUPUS GENLES Networks Anaya JM Bae SC Boackle SA Brown EE Chang DM Criswell LA Edberg JC Freedman BI Gregersen PK Gilkeson GS Jacob CO James JA Kamen DL Kimberly RP Martin J Merrill JT Niewold TB Park SY Petri MA Pons-Estel BA Ramsey-Goldman R Reveille JD Song YW Stevens AM Tsao BP Vila LM Vyse TJ Yu CY Guthridge JM Bruner GR Langefeld CD Montgomery C Harley JB 《American journal of human genetics》2011,88(1):3178-91
Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10(-8), OR = 0.83) and rs387619 (p = 7.7 × 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 × 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10(-3), OR = 0.81 and p = 4.3 × 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 × 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex. 相似文献
992.
Alexander Gusev S.?Hong Lee Gosia Trynka Hilary Finucane Bjarni?J. Vilhjálmsson Han Xu Chongzhi Zang Stephan Ripke Brendan Bulik-Sullivan Eli Stahl Schizophrenia Working Group of the Psychiatric Genomics Consortium SWE-SCZ Consortium Anna K. K?hler Christina M. Hultman Shaun M. Purcell Steven A. McCarroll Mark Daly Bogdan Pasaniuc Patrick F. Sullivan Benjamin M. Neale Naomi R. Wray Soumya Raychaudhuri Alkes L. Price 《American journal of human genetics》2014,95(5):535-552
Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs () across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of from imputed SNPs (5.1× enrichment; p = 3.7 × 10−17) and 38% (SE = 4%) of from genotyped SNPs (1.6× enrichment, p = 1.0 × 10−4). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease. 相似文献
993.
994.
Ullrich Köthe Frank Herrmannsdörfer Ilia Kats Fred A. Hamprecht 《Histochemistry and cell biology》2014,141(6):613-627
Although there are many reconstruction algorithms for localization microscopy, their use is hampered by the difficulty to adjust a possibly large number of parameters correctly. We propose SimpleSTORM, an algorithm that determines appropriate parameter settings directly from the data in an initial self-calibration phase. The algorithm is based on a carefully designed yet simple model of the image acquisition process which allows us to standardize each image such that the background has zero mean and unit variance. This standardization makes it possible to detect spots by a true statistical test (instead of hand-tuned thresholds) and to de-noise the images with an efficient matched filter. By reducing the strength of the matched filter, SimpleSTORM also performs reasonably on data with high-spot density, trading off localization accuracy for improved detection performance. Extensive validation experiments on the ISBI Localization Challenge Dataset, as well as real image reconstructions, demonstrate the good performance of our algorithm. 相似文献
995.
Emma Göthe Nikolai Friberg Maria Kahlert Johan Temnerud Leonard Sandin 《Biodiversity and Conservation》2014,23(1):63-80
With the current loss of biodiversity and threats to freshwater ecosystems, it is crucial to identify hot-spots of biodiversity and on which spatial scale they can be resolved. Conservation and management of these important ecosystems needs insight into whether most of the regional biodiversity (i.e. γ-diversity) can be found locally (i.e. high α-diversity) or whether it is distributed across the region (i.e. high β-diversity). Biodiversity patterns of benthic macroinvertebrates and diatoms were studied in 30 headwater streams in five Swedish catchments by comparing the relative contribution of α- and β-diversity to γ-diversity between two levels of stream habitat hierarchy (catchment and region level). The relationship between species community structure and local environmental factors was also assessed. Our results show that both α- and β-diversity made a significant contribution to γ-diversity. β-diversity remained relatively constant between the two levels of habitat hierarchy even though local environmental control of the biota decreased from the catchment to the region level. To capture most of headwater γ-diversity, management should therefore target sites that are locally diverse, but at the same time select sites so that β-diversity is maximized. As environmental control of the biota peaked at the catchment level, the conservation of headwater stream diversity is likely to be most effective when management targets environmental conditions across multiple local sites within relatively small catchments. 相似文献
996.
Maria R. Wing Wei Yang Valerie Teal Sankar Navaneethan Kaixiang Tao Akinlolu Ojo Nicolas N. Guzman Muredach Reilly Melanie Wolman Sylvia E. Rosas Magda Cuevas Michael Fischer Eva Lustigova Stephen R. Master Dawei Xie Dina Appleby Marshall Joffe John Kusek Harold I Feldman Dominic S. Raj for the Chronic Renal Insufficiency Cohort Study 《Obesity (Silver Spring, Md.)》2014,22(5):1359-1366
997.
998.
Helen Mason Azza Shoaibi Rula Ghandour Martin O'Flaherty Simon Capewell Rana Khatib Samer Jabr Belgin Unal Kaan S?zmen Chokri Arfa Wafa Aissi Habiba Ben Romdhane Fouad Fouad Radwan Al-Ali Abdullatif Husseini the MedCHAMPS project team 《PloS one》2014,9(1)
Background
Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey.Methods and Findings
Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia; $39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and $1,3000,000,000 and 378439 LYG in Turkey.Conclusion
Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives. 相似文献999.
Lungiswa Leonora Nkonki Emmanuelle Daviaud Debra Jackson Lumbwe Chola Tanya Doherty Mickey Chopra Bjarne Robberstad for the Promise-EBF Study Group 《PloS one》2014,9(1)
Background
Community-based peer support has been shown to be effective in improving exclusive breastfeeding rates in a variety of settings.Methods
We conducted a cost analysis of a community cluster randomised-controlled trial (Promise-EBF), aimed at promoting exclusive infant feeding in three sites in South Africa. The costs were considered from the perspective of health service providers. Peer supporters in this trial visited women to support exclusive infant feeding, once antenatally and four times postpartum.Results
The total economic cost of the Promise-EBF intervention was US$393 656, with average costs per woman and per visit of US$228 and US$52, respectively. The average costs per woman and visit in an operational ‘non research’ scenario were US$137 and US$32 per woman and visit, respectively. Investing in the promotion of exclusive infant feeding requires substantial financial commitment from policy makers. Extending the tasks of multi-skilled community health workers (CHWs) to include promoting exclusive infant feeding is a potential option for reducing these costs. In order to avoid efficiency losses, we recommend that the time requirements for delivering the promotion of exclusive infant feeding are considered when integrating it within the existing activities of CHWs.Discussion
This paper focuses on interventions for exclusive infant feeding, but its findings more generally illustrate the importance of documenting and quantifying factors that affect the feasibility and sustainability of community-based interventions, which are receiving increased focus in low income settings. 相似文献1000.
Patrick M. Chong Tarah Lynch Stuart McCorrister Pamela Kibsey Mark Miller Denise Gravel Garrett R. Westmacott Michael R. Mulvey the Canadian Nosocomial Infection Surveillance Program 《PloS one》2014,9(1)