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141.
Lisa Langsetmo Tuan V. Nguyen Nguyen D. Nguyen Christopher S. Kovacs Jerilynn C. Prior Jacqueline R. Center Suzanne Morin Robert G. Josse Jonathan D. Adachi David A. Hanley John A. Eisman the Canadian Multicentre Osteoporosis Study Research Group 《CMAJ》2011,183(2):E107-E114
Background
A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.Methods
We included participants aged 55–95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.Results
Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.Interpretation
The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.Current recommendations for the treatment of osteoporosis are in transition. The T-score-based definition of osteoporosis and osteopenia by the expert committee of the World Health Organization on bone mineral density has been used in many guidelines to set intervention thresholds for treatment. However, studies have consistently reported that the highest number of fractures in a given population occurs in those with osteopenic or normal bone mineral density.1,2 In fact, the National Osteoporosis Foundation has singled out people with osteopenic bone mineral density as a population in which assessment for fracture risk is merited.3Nevertheless, appropriate prevention and treatment strategies for such people are uncertain.4 Recent developments include the assessment of absolute fracture risk based on bone mineral density and other risk factors. Current Canadian methodology determines categorical risk based on age, sex, T-score, fracture history and glucocorticoid use.5 These criteria were derived from Swedish data, but have been assessed and validated in a cohort of Manitoba women.6 Newer nomograms based on the Australian cohort of the Dubbo Osteoporosis Epidemiology Study7 are now available for the calculation of low-trauma hip fracture8 and any fracture.9 These nomograms provide continuous estimates for five- and 10-year absolute fracture risk in both men and women (available at http://fractureriskcalculator.com). The use of factors in addition to bone mineral density may provide a better assessment of fracture risk for people who are near the T-score thresholds and facilitate decisions regarding therapeutic intervention.A key step in the development of any prediction model is the assessment of its validity.10 The aim of our study was to assess the performance of the Australian-derived nomogram among community-dwelling Canadians aged 55–95 years old. The first part of this assessment was a comparison of the nomogram model using the same variables, but using data from a Canadian population — participants in the Canadian Multicentre Osteoporosis Study (www.camos.org). The second part involved computing the calibration and discrimination of the nomogram in a Canadian cohort. The final part was comparison of the new assessments with the existing Canadian risk classification system. 相似文献142.
143.
目的探讨并行采集PAT技术(Parallel acquisition technique)对改善老年人肝脏磁共振扫描中出现的运动伪影的应用价值。方法对63例常规肝脏MRI检查出现呼吸运动伪影的老年患者(其中TrueFisp序列未出现明显伪影),行iPAT技术扫描(TrueFisp冠状位、T1 Flash轴位),对比常规序列扫描并评价iPAT技术对肝脏呼吸运动伪影消除的作用。三位磁共振专家对所得两组图像质量进行独立观察及评价,并进行对比分析。结果常规序列磁共振扫描63例肝脏呼吸运动伪影,其中Ⅰ、Ⅱ、Ⅲ和Ⅳ分别为0、15、33和15例,Ⅲ级以上影响诊断的病例共48例,占76%。采用iPAT技术扫描后,Ⅰ、Ⅱ、Ⅲ和Ⅳ分别为53、5、3和2例,Ⅲ级以下符合诊断要求的病例共58例,占92.1%,两者比较有显著差异(P〈0.05)。结论 iPAT技术可以明显缩短扫描的时间,在克服常规肝脏扫描中产生的呼吸运动伪影有明显的作用,可广泛应用于老年人肝脏常规检查产生的呼吸运动伪影校正中。 相似文献
144.
Karpova L S Popovtseva N M Stolyarova T P Stolyarov K A Mamadaliyev S M Khairullin B M Sandybayev N T Kydyrbayev Zh K Orynbayev M B Ospanov K S Baiserkin B S Boibosinov E U 《Virologica Sinica》2011,(5)
The aim of the work is the comparison of the epidemiology of influenza and acute respiratory virus infections (ARVI) in the Republic of Kazakhstan with the corresponding influenza epidemic in Russia induced by influenza pandemic virus A/California/07/2009 in 2009.Data on influenza and ARVI from the Republic of Kazakhstan and Federal Center of influenza was collected and investigated over the course of several weeks from hospitalized patients with the same diagnosis among all population and in age groups on ... 相似文献
145.
Bakker MF Verstappen SM Welsing PM Jacobs JW Jahangier ZN van der Veen MJ Bijlsma JW Lafeber FP;Utrecht Arthritis Cohort study group 《Arthritis research & therapy》2011,13(3):R70
Introduction
The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA). 相似文献146.
147.
Nica AC Parts L Glass D Nisbet J Barrett A Sekowska M Travers M Potter S Grundberg E Small K Hedman AK Bataille V Tzenova Bell J Surdulescu G Dimas AS Ingle C Nestle FO di Meglio P Min JL Wilk A Hammond CJ Hassanali N Yang TP Montgomery SB O'Rahilly S Lindgren CM Zondervan KT Soranzo N Barroso I Durbin R Ahmadi K Deloukas P McCarthy MI Dermitzakis ET Spector TD;MuTHER Consortium 《PLoS genetics》2011,7(2):e1002003
While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL), skin, and fat. The samples (156 LCL, 160 skin, 166 fat) were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes). In addition, we apply factor analysis (FA) to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes). The unique study design (Matched Co-Twin Analysis--MCTA) permits immediate replication of eQTLs using co-twins (93%-98%) and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20%) have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits. 相似文献
148.
International Parkinson's Disease Genomics Consortium 《PLoS genetics》2011,7(6):e1002142
A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson''s Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson''s disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10−10, PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci. 相似文献
149.
Tomlinson IP Carvajal-Carmona LG Dobbins SE Tenesa A Jones AM Howarth K Palles C Broderick P Jaeger EE Farrington S Lewis A Prendergast JG Pittman AM Theodoratou E Olver B Walker M Penegar S Barclay E Whiffin N Martin L Ballereau S Lloyd A Gorman M Lubbe S;COGENT Consortium;CORGI Collaborators;EPICOLON Consortium Howie B Marchini J Ruiz-Ponte C Fernandez-Rozadilla C Castells A Carracedo A Castellvi-Bel S Duggan D Conti D Cazier JB Campbell H Sieber O Lipton L Gibbs P Martin NG Montgomery GW 《PLoS genetics》2011,7(6):e1002105
Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases. 相似文献
150.
Oestergaard MZ Inoue M Yoshida S Mahanani WR Gore FM Cousens S Lawn JE Mathers CD;United Nations Inter-Agency Group for Child Mortality Estimation the Child Health Epidemiology Reference Group 《PLoS medicine》2011,8(8):e1001080