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排序方式: 共有665条查询结果,搜索用时 218 毫秒
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Eimear E. Kenny Alexander Gusev Kaitlin Riegel Dieter Lütjohann Jennifer K. Lowe Jacqueline Salit Julian B. Maller Markus Stoffel Mark J. Daly David M. Altshuler Jeffrey M. Friedman Jan L. Breslow Itsik Pe'er Ephraim Sehayek 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(33):13886-13891
Pinpointing culprit causal variants along signal peaks of genome-wide association studies (GWAS) is challenging. To overcome confounding effects of multiple independent variants at such a locus and narrow the interval for causal allele capture, we developed an approach that maps local shared haplotypes harboring a putative causal variant. We demonstrate our method in an extreme isolate founder population, the pacific Island of Kosrae. We analyzed plasma plant sterol (PPS) levels, a surrogate measure of cholesterol absorption from the intestine, where previous studies have implicated 2p21 mutations in the ATP binding cassette subfamily G members 5 or 8 (ABCG5 or ABCG8) genes. We have previously reported that 11.1% of the islanders are carriers of a frameshift ABCG8 mutation increasing PPS levels in carriers by 50%. GWAS adjusted for this mutation revealed genomewide significant signals along 11 Mb around it. To fine-map this signal, we detected pairwise identity-by-descent haplotypes using our tool GERMLINE and implemented a clustering algorithm to identify haplotypes shared across multiple samples with their unique shared boundaries. A single 526-kb haplotype mapped strongly to PPS levels, dramatically refining the mapped interval. This haplotype spans the ABCG5/ABCG8 genes, is carried by 1.8% of the islanders, and results in a striking 100% increase of PPS in carriers. Resequencing of ABCG5 in these carriers found a D450H missense mutation along the associated haplotype. These findings exemplify the power of haplotype analysis for mapping mutations in isolated populations and specifically for dissecting effects of multiple variants of the same locus. 相似文献
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Eimear Cleary Martin Boudou Patricia Garvey Coilin Oh Aiseadha Paul McKeown Jean ODwyer Paul Hynds 《Emerging infectious diseases》2021,27(9):2421
The Republic of Ireland regularly reports the highest annual crude incidence rates of Shiga toxin–producing Escherichia coli (STEC) enteritis in the European Union, ≈10 times the average. We investigated spatiotemporal patterns of STEC enteritis in Ireland using multiple statistical tools. Overall, we georeferenced 2,755 cases of infection during January 2013–December 2017; we found >1 case notified in 2,340 (12.6%) of 18,641 Census Small Areas. We encountered the highest case numbers in children 0–5 years of age (n = 1,101, 39.6%) and associated with serogroups O26 (n = 800, 29%) and O157 (n = 638, 23.2%). Overall, we identified 17 space-time clusters, ranging from 2 (2014) to 5 (2017) clusters of sporadic infection per year; we detected recurrent clustering in 3 distinct geographic regions in the west and mid-west, all of which are primarily rural. Our findings can be used to enable targeted epidemiologic intervention and surveillance. 相似文献
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Individuals typically adopt and prefer one or two learning styles and therefore, by default, remaining learning styles are underutilised. Insight into learning style preferences confers interpersonal benefits to both learners and teachers. Enlightened learners and teachers can identify their dominant learning styles and potentially strengthen underutilised ones. Findings from a retrospective study commissioned by Macmillan Cancer Relief that investigated learning style preferences of 137 female Macmillan Clinical Nurse Specialists (CNSs) showed that the majority (73.7%) displayed a strong-very strong preference for one or two learning styles. Mean scores across four learning styles were highest for the reflector learning style (mu=14.85+/-3.16) followed by theorist (mu=12.2+/-2.87), pragmatist (mu=11.5 (2.85) and activist (mu=7.95+/-3.11). An understanding of individual learning style preferences, particularly the strengthening of those that are underutilised is said to cultivate both flexible and resourceful learners and effective teachers. Such characteristics would confer considerable benefits within the remit of a Macmillan CNS position. 相似文献
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Marital status, quality of life, and clinical outcome in patients with heart failure 总被引:2,自引:0,他引:2
Luttik ML Jaarsma T Veeger N van Veldhuisen DJ 《Heart & lung : the journal of critical care》2006,35(1):3-8
AIM: This study investigated the impact of having a partner on quality of life (QoL), the number of hospital readmissions, and 9-month survival in patients with heart failure (HF). METHODS: The study population consisted of hospitalized patients with HF. QoL was measured by the Cantril Ladder of Life (0-10) during hospital admission. Clinical data, readmission rate, and number of deaths were registered by patient interview and chart review. RESULTS: Of the 179 patients, 96 (54%) were married or were living with a partner. Differences in QoL between married patients and those living alone were most pronounced with regard to future expectations of QoL (6.5 vs 5.0, P=.00). However, in a multivariate model QoL was primarily associated with socioeconomic status, age, and gender. Married patients had 12% less events in the 9-month follow-up period compared with patients living alone (P=not significant). CONCLUSION: This study indicates that most patients with HF who are living alone are mostly elderly women with a low socioeconomic status, who are at risk for recurrent events and a worse QoL. 相似文献