全文获取类型
收费全文 | 1053篇 |
免费 | 73篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 14篇 |
妇产科学 | 29篇 |
基础医学 | 169篇 |
口腔科学 | 14篇 |
临床医学 | 133篇 |
内科学 | 206篇 |
皮肤病学 | 16篇 |
神经病学 | 95篇 |
特种医学 | 53篇 |
外科学 | 81篇 |
综合类 | 7篇 |
预防医学 | 155篇 |
眼科学 | 10篇 |
药学 | 78篇 |
肿瘤学 | 64篇 |
出版年
2024年 | 2篇 |
2023年 | 30篇 |
2022年 | 29篇 |
2021年 | 70篇 |
2020年 | 38篇 |
2019年 | 35篇 |
2018年 | 39篇 |
2017年 | 29篇 |
2016年 | 34篇 |
2015年 | 35篇 |
2014年 | 45篇 |
2013年 | 58篇 |
2012年 | 94篇 |
2011年 | 81篇 |
2010年 | 44篇 |
2009年 | 50篇 |
2008年 | 58篇 |
2007年 | 67篇 |
2006年 | 60篇 |
2005年 | 49篇 |
2004年 | 44篇 |
2003年 | 33篇 |
2002年 | 29篇 |
2001年 | 1篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有1128条查询结果,搜索用时 15 毫秒
1.
The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice 总被引:1,自引:0,他引:1
Hans-Peter R. Bootsma †Albert P. Aldenkamp Leonie Diepman Jacques Hulsman Danielle Lambrechts Loes Leenen Marian Majoie Ad Schellekens †Marc de Krom 《Epilepsia》2006,47(S2):24-27
Summary: Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
2.
Werner I Hagens Peter Olinga Dirk K F Meijer Geny M M Groothuis Leonie Beljaars Klaas Poelstra 《Liver international》2006,26(2):232-239
BACKGROUND: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver. METHODS: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell-cell interactions are preserved, which closely mimics the in vivo situation. RESULTS: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected. CONCLUSIONS: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects. 相似文献
3.
The aim of this study was to investigate insurance records for a one-year period to determine the injury frequencies and costs associated with different age groups in netball. The insurance records for all netball claims made during 1999 in Victoria were obtained from the insurer and entered into a database. The overall injury rate was 9.49 injuries per 1000 players, with 829 claims for injuries filed with the insurance company. Of all injuries claimed for, 85.3% were to the lower limb, 8.7% to the upper limb, 3.1% to the spine/torso and 2.9% to the head and face. Lower limb injuries accounted for 85.4% of costs, upper limb injuries 10.7% and head/neck/torso injuries 3.9% of total injury costs. Knee injuries accounted for 56.9% of total costs, with ankle and calf/Achilles injuries costing 12.7 and 11.8% of total costs, respectively. Injury prevention strategies should therefore be directed to three main injuries taking into account costs and incidence. These injuries were: ankle sprains, knee ligament sprains and Achilles tendon strains. Specifically, the prevention program for Achilles injuries should be directed to the >25 years age groups. 相似文献
4.
5.
6.
Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains 总被引:10,自引:0,他引:10
Huber TB Simons M Hartleben B Sernetz L Schmidts M Gundlach E Saleem MA Walz G Benzing T 《Human molecular genetics》2003,12(24):3397-3405
Hereditary nephrotic syndrome is a heterogeneous disease, characterizedby heavy proteinuria and renal failure. Mutations of NPHS1 orNPHS2, the genes encoding for nephrin and podocin, lead to earlyonset of heavy proteinuria, and rapid progression to end-stagerenal disease, suggesting that both proteins are essential forthe integrity of the glomerular filter. Podocin is a stomatinprotein family member with a predicted hairpin-like structurelocalizing to the insertion site of the slit diaphragm of podocytes,the visceral glomerular epithelial cells of the kidney. Herewe investigate the pathomechanisms of different disease-causingpodocin mutations. We show that wild-type podocin is targetedto the plasma membrane, and forms homo-oligomers involving thecarboxy and amino terminal cytoplasmic domains. The associationof podocin with specialized lipid raft microdomains of the plasmamembrane was a prerequisite for recruitment of nephrin intorafts. In contrast, disease-causing mutations of podocin (R138Qand R138X) failed to recruit nephrin into rafts either becausethese mutants were retained in the endoplasmic reticulum (R138Q),or because they failed to associate with rafts (R138X) despitetheir presence in the plasma membrane. None of the mutants didaugment nephrin signaling, suggesting that lipid raft targetingfacilitates nephrin signaling. Our findings demonstrate thatthe failure of mutant podocin to recruit nephrin into lipidrafts may be essential for the pathogenesis of NPHS2.
* To whom correspondence should be addressed. Tel: +49 7612703559;Fax: +49 7612706362; Email: benzing{at}med1.ukl.uni-freiburg.de
相似文献
7.
Benjamin J Baig Anna Beaglehole Robert C Stewart Leonie Boeing Douglas H Blackwood Johan Leuvennink Felix Kauye 《BMC medical education》2008,8(1):23
Background
International reports recommend the improvement in the amount and quality of training for mental health workers in low and middle income countries. The Scotland-Malawi Mental Health Education Project (SMMHEP) has been established to support the teaching of psychiatry to medical students in the University of Malawi. While anecdotally supportive medical educational initiatives appear of value, little quantitative evidence exists to demonstrate whether such initiatives can deliver comparable educational standards. This study aimed to assess the effectiveness of an undergraduate psychiatry course given by UK psychiatrists in Malawi by studying University of Malawi and Edinburgh University medical students' performance on an MCQ examination paper. 相似文献8.
van Eden W Hauet-Broere F Berlo S Paul L van der Zee R de Kleer I Prakken B Taams L 《International reviews of immunology》2005,24(3-4):181-197
Immunization with microbial or mammalian stress proteins or heat-shock proteins in models of experimental autoimmunity has been observed to lead to increased disease resistance. Furthermore, such immunization has been proposed to result in the induction and expansion of T cells that suppress disease upon transfer. Comparisons of microbial heat-shock proteins with other conserved immunogenic proteins of bacterial origin have indicated a unique capacity for heat-shock proteins to induce a regulatory phenotype in T cells, such as reflected by the production of IL10. Also, studies in children with chronic arthritis have indicated that T-cell responses to heat-shock proteins are associated with a benign course of the disease and with remission. Furthermore, in patients, heat-shock-protein-(HSP-) activated T cells were shown to display regulatory phenotypes consistent with CD4+ CD25+ T regulatory cells. 相似文献
9.
Taams LS Vukmanovic-Stejic M Smith J Dunne PJ Fletcher JM Plunkett FJ Ebeling SB Lombardi G Rustin MH Bijlsma JW Lafeber FP Salmon M Akbar AN 《European journal of immunology》2002,32(6):1621-1630
Anergic/suppressive CD4+CD25+ T cells have been proposed to play an important role in the maintenance of peripheral tolerance. Here we demonstrate that in humans these cells suppress proliferation to self antigens, but also to dietary and foreign antigens. The suppressive CD4+CD25+ T cells display a broad usage of the T cell receptor Vbeta repertoire,suggesting that they recognize a wide variety of antigens. They reside in the primed/memory CD4+CD45RO+CD45RB(low) subset and have short telomeres, indicating that these cells have the phenotype of highly differentiated CD4+ T cells that have experienced repeated episodes of antigen-specific stimulation in vivo. This suggests that anergic/suppressive CD4+CD25+ T cells may be generated in the periphery as a consequence of repeated antigenic encounter. This is supported by the observation that highly differentiated CD4+T cells can be induced to become anergic/suppressive when stimulated by antigen presented by non-professional antigen-presenting cells. We suggest that besides being generated in the thymus, CD4+CD25+ regulatory T cells may also be generated in the periphery. This would provide a mechanism for the generation of regulatory cells that induce tolerance to a wide array of antigens that may not be encountered in the thymus. 相似文献
10.
Kirsten Mehlig Christopher Holmberg Leonie H. Bogl Eva Erhardt Charalambos Hadjigeorgiou Antje Hebestreit Jaakko Kaprio Fabio Lauria Nathalie Michels Iris Pigeot Lucia A. Reisch Toomas Veidebaum Lauren Lissner 《Obesity facts》2021,14(1):121
BackgroundDuring adolescence, health behaviors and weight status are increasingly influenced by friendship and peer networks. This paper examines resemblances in weight-related characteristics and how they differ by sociodemographic factors.MethodsOver 3,000 friendships were reported by 1,603 adolescents, aged 11–16 years, who participated in the school-based I. Family study in 6 European countries. Each “source child” named 1–10 friends for whom standardized weight-related traits were available in the same survey. The mean value of the friends'' traits weighted by time spent together was calculated, and related to the source child''s trait. Country, age and sex of the source child, parental education, and immigrant background were considered for confounding and moderation.ResultsSource children''s z-scores of body fat percent and BMI were positively associated with their friends'' characteristics, in particular if they had highly educated parents. Positive associations were also found regarding the frequency of fast-food consumption, impulsivity, screen time, preference for sugar-sweetened foods, and hours spent in sports clubs, in increasing order of effect size. Additionally, correlations were observed between friends'' cognitive and school functioning and being bullied. No associations were seen for a preference for high-fat foods, weight concerns, and health-related quality of life. Finally, parental education and immigrant background were associated between friends in all countries except Sweden, where no associations were observed.ConclusionAdolescent friends shared a number of weight-related characteristics. For weight measures per se, positive associations with friends'' characteristics were only observed in adolescents with high parental education. Associations regarding energy-balance behaviors and indicators of school-related well-being did not differ by parental education. Parental education and immigrant background correlated positively in friends in most countries showing that social aggregation is already occurring in adolescence. The wide spectrum of friendship associations in weight-related traits and behaviors suggests that health promotion initiatives in adolescents should be directed towards peer groups in both school-related and leisure-time environments.ISRCTN RegistryPan-European IDEFICS/I. Family children cohort (ID ISRCTN62310987; https://doi.org/10.1186/ISRCTN62310987). 相似文献