全文获取类型
收费全文 | 1656篇 |
免费 | 124篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 51篇 |
儿科学 | 36篇 |
妇产科学 | 50篇 |
基础医学 | 270篇 |
口腔科学 | 20篇 |
临床医学 | 135篇 |
内科学 | 421篇 |
皮肤病学 | 27篇 |
神经病学 | 163篇 |
特种医学 | 28篇 |
外科学 | 97篇 |
综合类 | 17篇 |
一般理论 | 1篇 |
预防医学 | 154篇 |
眼科学 | 27篇 |
药学 | 173篇 |
中国医学 | 1篇 |
肿瘤学 | 117篇 |
出版年
2024年 | 2篇 |
2023年 | 36篇 |
2022年 | 124篇 |
2021年 | 179篇 |
2020年 | 71篇 |
2019年 | 80篇 |
2018年 | 90篇 |
2017年 | 63篇 |
2016年 | 81篇 |
2015年 | 78篇 |
2014年 | 73篇 |
2013年 | 110篇 |
2012年 | 153篇 |
2011年 | 144篇 |
2010年 | 65篇 |
2009年 | 52篇 |
2008年 | 81篇 |
2007年 | 70篇 |
2006年 | 73篇 |
2005年 | 59篇 |
2004年 | 36篇 |
2003年 | 34篇 |
2002年 | 24篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有1788条查询结果,搜索用时 15 毫秒
21.
Karolina Sikorska Nahid Mostafavi Montazeri André Uitterlinden Fernando Rivadeneira Paul HC Eilers Emmanuel Lesaffre 《European journal of human genetics : EJHG》2015,23(10):1384-1391
Analysis of genome-wide association studies with longitudinal data using standard procedures, such as linear mixed model (LMM) fitting, leads to discouragingly long computation times. There is a need to speed up the computations significantly. In our previous work (Sikorska et al: Fast linear mixed model computations for genome-wide association studies with longitudinal data. Stat Med 2012; 32.1: 165–180), we proposed the conditional two-step (CTS) approach as a fast method providing an approximation to the P-value for the longitudinal single-nucleotide polymorphism (SNP) effect. In the first step a reduced conditional LMM is fit, omitting all the SNP terms. In the second step, the estimated random slopes are regressed on SNPs. The CTS has been applied to the bone mineral density data from the Rotterdam Study and proved to work very well even in unbalanced situations. In another article (Sikorska et al: GWAS on your notebook: fast semi-parallel linear and logistic regression for genome-wide association studies. BMC Bioinformatics 2013; 14: 166), we suggested semi-parallel computations, greatly speeding up fitting many linear regressions. Combining CTS with fast linear regression reduces the computation time from several weeks to a few minutes on a single computer. Here, we explore further the properties of the CTS both analytically and by simulations. We investigate the performance of our proposal in comparison with a related but different approach, the two-step procedure. It is analytically shown that for the balanced case, under mild assumptions, the P-value provided by the CTS is the same as from the LMM. For unbalanced data and in realistic situations, simulations show that the CTS method does not inflate the type I error rate and implies only a minimal loss of power. 相似文献
22.
Jargalsaikhan Dagvadorj Karolina Mikulska-Ruminska Gantsetseg Tumurkhuu Rojo A. Ratsimandresy Jessica Carriere Allen M. Andres Stefanie Marek-Iannucci Yang Song Shuang Chen Malcolm Lane Andrea Dorfleutner Roberta A. Gottlieb Christian Stehlik Suzanne Cassel Fayyaz S. Sutterwala Ivet Bahar Timothy R. Crother Moshe Arditi 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(1)
23.
Hong Li Christopher Lelliott Karolina Ploj Martina Verolin-Johansson Björn Carlsson Erik Michaëlsson 《Metabolism: clinical and experimental》2008,57(12):1704-1710
Chronic inflammation and increased visceral adipose tissue (VAT) are key elements of the metabolic syndrome. Both are considered to play a pathogenic role in the development of liver steatosis and insulin resistance. The aim of the present study was to investigate the hypothesis that an inflamed intestine, induced both by diet and chemical irritation, could induce persistent inflammation in VAT. Female C57BL/6JOlaHsd mice were used. In study I, groups of mice (n = 6 per group) were given an obesity-inducing cafeteria diet (diet-induced obesity) or regular chow only (control) for 14 weeks. In study II, colitis in mice (n = 8) was induced by 3% dextran sulfate sodium in tap water for 5 days followed by 21 days of tap water alone. Healthy control mice (n = 8) had tap water only. At the end of the studies, all mice were killed; and blood and tissues were sampled and processed for analysis. Body weight of diet-induced obese mice was greatly increased, with evidence of systemic inflammation, insulin resistance, and liver steatosis. Tissue inflammation indexed by proinflammatory cytokine expression was recorded in liver, mesenteric fat, and proximal colon/distal ileum, but not in subcutaneous or perigonadal fat. In dextran sulfate sodium-induced colitis mice, mesenteric fat was even more inflamed than the colon, whereas a much milder inflammation was seen in liver and subcutaneous fat. The studies showed both diet- and colitis-initiated inflammation in mesenteric fat. Fat depots contiguous with intestine and their capacity for exaggerated inflammatory responses to conditions of impaired gut barrier function may account for the particularly pathogenic role of VAT in obesity-induced metabolic disorders. 相似文献
24.
Alicja Nowak Karolina Przybylowska-Sygut Mira Gacek Anna Kaminska Jacek P. Szaflik Jerzy Szaflik 《Ophthalmic genetics》2015,36(2):105-112
Background: Glaucoma is characterized by optic neuropathy of the retinal ganglion cell. It may be possible that β-amyloid (Aβ) and apolipoprotein E (APOE), the main proteins of the pathogenesis of AD, play a role in glaucoma development. The aim of this study was to evaluate a relationship between the APP and APOE gene polymorphisms and the risk of primary open-angle glaucoma (POAG) occurrence.Materials and methods: The study consisted of 183 patients with POAG and 209 healthy subjects. Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP.Results: We found a statistically significant increase of the -491?T allele frequency (p?=?0.02; OR?=?1.48; 95% CI?=?1.06–2.08) of APOE in POAG compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the APP polymorphism between patients and controls group. We also found an association between APOE polymorphic variant and retinal nerve fiber layer (RNFL). There was a statistically significant difference in the APOE gene A/T genotype frequency in the early POAG stage and middle-advanced POAG stage in comparison to the advanced POAG stage (p?=?0.04; OR?=?3.38; 95% CI?=?1.04–10.97).Conclusions: The -491?T allele of APOE polymorphism may be associated with a risk of POAG occurrence in the Polish population. 相似文献
25.
Lukasova Vera Buzgo Matej Vocetkova Karolina Kubíkov Tereza Tonar Zbynk Doupnik Miroslav Blahnova Veronika Litvinec Andrej Sovkova Vera Voltrov Barbora Staffa Andrea Svora Petr Kralickova Milena Amler Evzen Filova Eva Rustichelli Franco Rampichova Michala 《RSC advances》2018,8(39):21889
Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. 相似文献
26.
27.
Tiffany Thomas Francesca Cendali Xiaoyun Fu Fabia Gamboni Evan J. Morrison Jonathan Beirne Travis Nemkov Marianna H. Antonelou Anastasios Kriebardis Ian Welsby Ariel Hay Karolina H. Dziewulska Michael P. Busch Steven Kleinman Paul W. Buehler Steven L. Spitalnik James C. Zimring Angelo D'Alessandro 《Transfusion》2021,61(6):1867-1883
28.
Edhom Karolina af Lidman Christer Granberg Tobias Taylor Graham P. Paucar Martin 《Journal of neurovirology》2021,27(2):345-347
Journal of NeuroVirology - Human T-lymphotropic virus type-1 (HTLV-1) is a neglected infection most often associated with an indolent process. However, a subset of HTLV-1 seropositive patients face... 相似文献
29.
Magorzata Mizerska-Wasiak Dominika Adamczuk Karolina Cicho-Kawa Monika Miklaszewska Hanna Szymanik-Grzelak Jacek A. Pietrzyk Agnieszka Pukajo-Marczyk Danuta Zwoliska Agnieszka Rybi-Szumiska Anna Wasilewska Beata Bienia Przemysaw Sikora Agnieszka Firszt-Adamczyk Roman Stankiewicz Maria Szczepaska Magorzata Paczyk-Tomaszewska 《Archives of Medical Science》2021,17(1):84
IntroductionImmunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence.Material and methodsThe multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence.ResultsMean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL.ConclusionsWe found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group. 相似文献
30.
Amanda Karolina Soares e Silva Dilênia de Oliveira Cipriano Torres Sura Wanessa Santos Rocha Fabiana Oliveira dos Santos Gomes Bruna dos Santos Silva Mariana Aragão Matos Donato Catarina Raposo Ana Célia Oliveira Santos Maria do Carmo Alves de Lima Suely Lins Galdino Ivan da Rocha Pitta José Roberto Botelho de Souza Christina Alves Peixoto 《Cardiovascular pathology》2013,22(1):81-90
BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis. 相似文献