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71.
The Genome Search Meta-Analysis (GSMA) method is widely used to detect linkage by pooling results of previously published genome-wide linkage studies. The GSMA uses a non-parametric summed rank statistic in 30 cM bins of the genome. Zintzaras and Ioannidis ([2005] Genet. Epidemiol. 28:123-137) developed a method of testing for heterogeneity of evidence for linkage in the GSMA, with three heterogeneity statistics (Q, Ha, B). They implement two testing procedures, restricted versus unrestricted for the summed rank within the bin. We show here that the rank-unrestricted test provides a conservative test for high heterogeneity and liberal test for low heterogeneity in linked regions. The rank-restricted test should therefore be used, despite the extensive simulations needed. In a simulation study, we show that the power to detect heterogeneity is low. For 20 studies of affected sib pairs, simulated assuming linkage in all studies to a gene with sibling relative risk of 1.3, the power to detect low heterogeneity using the Q statistic was 14%. With linkage present in 50% of the studies (to a gene with sibling relative risk of 1.4), the Q heterogeneity statistic had power of 29% to detect high heterogeneity. The power to detect linkage using the summed rank was high in both of these situations, at 98% and 79%, respectively. Although testing for heterogeneity in the GSMA is of interest, the currently available method provides little additional information to that provided by the summed rank statistic. 相似文献
72.
Yvonne Millar Danya Glaser Natalie L. Reilly‐Johnson Sarah‐Louise Hurst Kelly Harris Cathryn Skerry Tony Charman 《Child and Adolescent Mental Health》2010,15(3):134-141
Background: The NIPPERS (Nursery Intervention Project for Parents & Education Related Services) was a novel community psychology service based in nursery settings in socio‐economically disadvantaged, inner‐city areas in London. Method: The service included consultation work with nursery staff, structured parenting groups and individual sessions for parents. Results: The delivery of the clinical service and research evaluation underwent several changes in the first phase of the project, in particular to ensure that the service was acceptable and accessible to families and staff. Although take‐up of community services was higher than in the local clinic‐based services, it was not taken up by some 40% of parents. Due to the allocation design, it was not possible to measure the effectiveness of the intervention. Conclusions: The NIPPERS service was successful in delivering a community child psychology service to families with high levels of early child behavioural problems at high risk for continuing difficulties. 相似文献
73.
Cathryn L. Abbott Daniel Ebert Amy Tabata Thomas W. Therriault 《Conservation Genetics Resources》2011,3(1):79-81
454 pyrosequencing reads were used to isolate microsatellites in the global marine ascidian invader, Didemnum vexillum. This method allows simple and cost-effective isolation of new markers from organisms without existing genomic information and, to our knowledge, has not been used before to develop a polymorphic microsatellite marker set. Loci had between two and eleven alleles and overall mean observed and expected heterozygosities of 0.57 and 0.62, respectively. These markers will greatly facilitate research required to develop control and mitigation strategies for D. vexillum. 相似文献
74.
Cathryn M. Kolka 《Clinical and experimental pharmacology & physiology》2020,47(1):168-175
The endocrine system relies on the vasculature for delivery of hormones throughout the body, and the capillary microvasculature is the site where the hormones cross from the blood into the target tissue. Once considered an inert wall, various studies have now highlighted the functions of the capillary endothelium to regulate transport and therefore affect or maintain the interstitial environment. The role of the capillary may be clear in areas where there is a continuous endothelium, yet there also appears to be a role of endothelial cells in tissues with a sinusoidal structure. Here we focused on the most common endocrine disorder, diabetes, and several of the target organs associated with the disease, including skeletal muscle, liver and pancreas. However, it is important to note that the ability of hormones to cross the endothelium to reach their target tissue is a component of all endocrine functions. It is also a consideration in organs throughout the body and may have greater impact for larger hormones with target tissues containing a continuous endothelium. We noted that the blood levels do not always equal interstitial levels, which is what the cells are exposed to, and discussed how this may change in diseases such as obesity and insulin resistance. The capillary endothelium is, therefore, an essential and understudied aspect of endocrinology and metabolism that can be altered in disease, which may be an appropriate target for treatment. 相似文献
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77.
Neurodegenerative diseases are an ever-increasing burden in an aging society.Currently no cure is available for any of these diseases and treatment is based on managing symptoms.Despite many candidate therapeutics demonstrating promise in animal models,none has yet shown efficacy in human trials.It is self-evident that humans are different from the animals used to model our diseases,especially models that have been highly manipulated to generate a disease in an animal that does not naturally have such a disease.These differences are likely the reason for the failures of drug candidates in human trials but,until recently,human models of neurodegenerative diseases were lacking.The development of the human cerebral organoid model,by differentiating three-dimensional human neuronal tissue from pluripotent stem cells,represents a significant advance in studying human brain diseases.Cerebral organoids have been used to model Alzheimer’s disease,Parkinson’s disease,Down’s syndrome dementia and we have now shown they can be infected with human prions creating a new model of human prion diseases. 相似文献
78.
John P A Ioannidis Mandy Y Ng Pak C Sham Elias Zintzaras Cathryn M Lewis Hong-Wen Deng Michael J Econs David Karasik Marcella Devoto Candace M Kammerer Tim Spector Toby Andrew L Adrienne Cupples Emma L Duncan Tatiana Foroud Douglas P Kiel Daniel Koller Bente Langdahl Braxton D Mitchell Munro Peacock Robert Recker Hui Shen Katia Sol-Church Loretta D Spotila Andre G Uitterlinden Scott G Wilson Annie W C Kung Stuart H Ralston 《Journal of bone and mineral research》2007,22(2):173-183
Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. 相似文献
79.
Carol Bower Lynda Blum Kevin O'Daly Cathryn Higgins Francis Loutsky Christopher Kosky 《Australian and New Zealand journal of public health》1997,21(7):716-721
Abstract: To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child–bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child–bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993. ( Aust N Z J Public Health 1997; 21: 716–21) 相似文献
80.