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81.
Brian P. McEvoy Grant W. Montgomery Allan F. McRae Samuli Ripatti Markus Perola Tim D. Spector Lynn Cherkas Kourosh R. Ahmadi Dorret Boomsma Gonneke Willemsen Jouke J. Hottenga Nancy L. Pedersen Patrik K.E. Magnusson Kirsten Ohm Kyvik Kaare Christensen Jaakko Kaprio Kauko Heikkil? Aarno Palotie Elisabeth Widen Juha Muilu Ann-Christine Syv?nen Ulrika Liljedahl Orla Hardiman Simon Cronin Leena Peltonen Nicholas G. Martin Peter M. Visscher 《Genome research》2009,19(5):804-814
Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.Patterns of genetic variation within and between human populations have long provided novel insights into the origin and history of different groups. The advent of whole genome association (WGA) mapping has also highlighted the practical importance of identifying and understanding these patterns. A mismatch in the ancestry of individuals in a simple case/control association paradigm can lead to false positives and/or reduced power to detect associations.Studies of population-level whole genome (WG) polymorphism were initially restricted to the International HapMap populations (Yoruban, Japanese, Chinese, and European-Americans) but provided valuable information on intercontinental variation across the human genome, including structural variation, recombination, and selection (International HapMap Consortium 2005, 2007). The whole genome approach has now begun to be applied to more nuanced intracontinental variation within Europe. First generation studies using European-Americans or small numbers of in situ Europeans (but with relatively few markers) quickly identified a clear North–South split in the continent''s population and hinted at further structure (Seldin et al. 2006; Bauchet et al. 2007; Price et al. 2008; Seldin and Price 2008; Tian et al. 2008). Analysis of WG variation in larger numbers of individuals sampled in situ from multiple European populations has recently extended these findings. Using principal component analysis (PCA) of up to ≈300,000 SNPs, they have shown a remarkable correlation of an individual''s position in genetic space to their geographic origin (Heath et al. 2008; Lao et al. 2008; Novembre et al. 2008).We continue this progression by exploring subcontinental WG (300K) variation in 2099 individuals from six Northern European populations (Ireland, United Kingdom, Netherlands, Sweden, Denmark, and Finland), as well as two descendent New World populations (European-Australians and the European-American HapMap sample). The data demonstrate and confirm an ability to dissect regional to subregional geographic structure and also point to the discernable impact of differential natural selection on the recently diverged Northern European populations. Both of these observations have important present-day consequences in explaining disease incidence and in mapping complex traits through association methods. 相似文献
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Danielle Posthuma Dirk‐Jan de Koning Conor Dolan Michael E. Goddard Peter M. Visscher 《Genetic epidemiology》2009,33(8):710-716
The genetic dissection of quantitative traits, or endophenotypes, usually involves genetic linkage or association analysis in pedigrees and subsequent fine mapping association analysis in the population. The ascertainment procedure for quantitative traits often results in unequal variance of observations. For example, some phenotypes may be clinically measured whilst others are from self‐reports, or phenotypes may be the average of multiple measures but with the number of measurements varying. The resulting heterogeneity of variance poses no real problem for analysis, as long as it is properly modelled and thereby taken into account. However, if statistical significance is determined using an empirical permutation procedure, it is not obvious what the units of sampling are. We investigated a number of permutation approaches in a simulation study of an association analysis between a quantitative trait and a single nucleotide polymorphism. Our simulations were designed such that we knew the true p‐value of the test statistics. A number of permutation methods were compared from the regression of true on empirical p‐values and the precision of the empirical p‐values. We show that the best procedure involves an implicit adjustment of the original data for the effects in the model before permutation, and that other methods, some of which seemed appropriate a priori, are relatively biased. Genet. Epidemiol. 33:710–716, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Ilkay Evren Elisabeth R. Brouns Jos B. Poell Leon J. Wils Ruud H. Brakenhoff Elisabeth Bloemena Jan G.A.M. de Visscher 《Oral diseases》2023,29(2):696-706
Objectives
To identify possible associations between patients’ demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients’ first visit.Method
A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated.Results
A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size <2cm and non-homogeneous OLs (42%) with non-smokers. No dysplasia was present in 40% and any dysplasia (AD) in 60%. Tongue OLs were correlated with AD (OR:6.0) and CD (OR:5.7). FOM OLs were correlated with CD (OR:4.5). DD was correlated with non-homogeneous OLs (OR:2.6).Conclusions
CD was most frequently observed in tongue and FOM OLs, while DD was associated with non-homogeneous OLs. In this series of patients, there was no consistent reliable association between the clinical and histopathological features and clinical characteristics can therefore not substitute microscopic examination of biopsies. 相似文献87.
Jos B. Poell Leon J. Wils Arjen Brink Ralf Dietrich Christine Krieg Eunike Velleuer Ilkay Evren Elisabeth R. Brouns Jan G. de Visscher Elisabeth Bloemena Bauke Ylstra Ruud H. Brakenhoff 《International journal of cancer. Journal international du cancer》2023,152(2):227-238
Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient. 相似文献
88.
Oral mixing ability and cognition in elderly persons with dementia: A cross‐sectional study 下载免费PDF全文
R. A. F. Weijenberg F. Lobbezoo C. M. Visscher E. J. A. Scherder 《Journal of oral rehabilitation》2015,42(7):481-486
Masticatory performance has been positively associated with cognitive ability in both animals and healthy humans. We hypothesised that there would also be a positive correlation between masticatory performance and cognition in older persons suffering from dementia. Older persons suffering from dementia (n = 114) and receiving institutionalised care were studied in a cross‐sectional design. The assessments included masticatory performance, which was measured objectively with a two‐colour gum mixing ability test, and cognition, which was assessed with a multidomain neuropsychological test battery. Significant relationships were observed between masticatory performance and general cognition and between masticatory performance and verbal fluency. Hierarchical regression analysis revealed that the correlation with general cognition was influenced by the scores for dependency in activities of daily living. The association between verbal fluency and masticatory performance was not significantly affected by secondary variables. An unexpected limitation of this study was the high dropout rate for the mixing ability test. The clinical implications of these findings are profound; care professionals should endeavour to maintain and stimulate mastication in older persons with dementia in an attempt to preserve cognition. 相似文献
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Erik Scherder Laura EggermontChris Visscher Philip ScheltensDick Swaab 《Neuroscience and biobehavioral reviews》2011,35(3):699-714
Predicting and anticipating disturbances in higher level gait is particularly relevant for patients with dementia as higher level gait appears to be closely related to higher level cognitive functioning. A phenomenon that could contribute to the understanding and prediction of disturbances in higher level gait and gait-related motor activity in the various subtypes of dementia is paraphrased as ‘last in-first out’. ‘Last in-first out’ refers to the principle that neural circuits that mature late in development are the most vulnerable to neurodegeneration. The strength of relating symptoms to the ‘last in-first out’ principle is that a future symptom can be predicted and anticipated in a therapeutic way, even if the disease process has not already started.Therefore, the aim of this review is to provide new strategies for rehabilitation of higher level gait disturbances in dementia based upon the ‘last in-first out’ principle. These new strategies emerge from five neural networks: the superior longitudinal fasciculus, the uncinate fasciculus, the fronto-cerebellar and fronto-striatal connections, and the cingulum. 相似文献