全文获取类型
收费全文 | 476篇 |
免费 | 38篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 8篇 |
妇产科学 | 6篇 |
基础医学 | 97篇 |
口腔科学 | 9篇 |
临床医学 | 45篇 |
内科学 | 80篇 |
皮肤病学 | 12篇 |
神经病学 | 52篇 |
特种医学 | 13篇 |
外科学 | 31篇 |
综合类 | 3篇 |
一般理论 | 2篇 |
预防医学 | 46篇 |
眼科学 | 15篇 |
药学 | 47篇 |
中国医学 | 4篇 |
肿瘤学 | 47篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 13篇 |
2021年 | 40篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 27篇 |
2017年 | 10篇 |
2016年 | 26篇 |
2015年 | 26篇 |
2014年 | 37篇 |
2013年 | 40篇 |
2012年 | 45篇 |
2011年 | 47篇 |
2010年 | 22篇 |
2009年 | 20篇 |
2008年 | 28篇 |
2007年 | 22篇 |
2006年 | 19篇 |
2005年 | 13篇 |
2004年 | 16篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有518条查询结果,搜索用时 15 毫秒
41.
Campa D Hüsing A Chang-Claude J Dostal L Boeing H Kröger J Tjønneland A Roswall N Overvad K Dahm CC Rodríguez L Sala N Pérez MJ Larrañaga N Chirlaque MD Ardanaz E Khaw KT Wareham N Allen NE Travis RC Trichopoulou A Naska A Bamia C Palli D Sieri S Tumino R Sacerdote C van Kranen HJ Bas Bueno-de-Mesquita H Stattin P Johansson M Chajes V Rinaldi S Romieu I Siddiq A Norat T Riboli E Kaaks R Canzian F 《European journal of cancer (Oxford, England : 1990)》2011,47(3):420-427
A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk. 相似文献
42.
Insa M.A. Ernst Anika E. Wagner Christine Schuemann Niels Storm Wolfgang Höppner Frank Döring Achim Stocker Gerald Rimbach 《Pharmacological research》2011,63(3):233-240
The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts. 相似文献
43.
Hinners I Hill A Otto U Michalsky A Mack TG Striggow F 《Molecular and cellular neurosciences》2008,37(3):559-567
A better understanding of the cellular and molecular pathomechanisms of Alzheimer's disease (AD) is a prerequisite for the development of efficient treatments. We have used a novel assay system based on virus-transduced organotypic hippocampal slice cultures that mimics important aspects of tau-driven AD pathology in a short time frame. Human tau P301L, when expressed in pyramidal neurons of hippocampal slice cultures, was increasingly phosphorylated at several disease-relevant epitopes, leading to progressive neuronal dystrophy and formation of RIPA-insoluble tau. AD-like tau hyperphosphorylation was reduced by the tau kinase inhibitors lithium and SRN-003-556, but RIPA-insoluble tau remained unaffected after treatment with any of these substances. Only SRN-003-556 was able to protect hippocampal neurons from synaptic damage that was presumably caused by a toxic soluble tau fraction. These data provide first mechanistic insights towards the functional benefits of SRN-003-556 that have been observed in vivo. 相似文献
44.
45.
46.
Eckert A Kloor M Giersch A Ahmadi R Herold-Mende C Hampl JA Heppner FL Zoubaa S Holinski-Feder E Pietsch T Wiestler OD von Knebel Doeberitz M Roth W Gebert J 《Brain pathology (Zurich, Switzerland)》2007,17(2):146-150
About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (approximately 25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms. 相似文献
47.
Kaneider NC Leger AJ Agarwal A Nguyen N Perides G Derian C Covic L Kuliopulos A 《Nature immunology》2007,8(12):1303-1312
Sepsis is a deadly disease characterized by considerable derangement of the proinflammatory, anti-inflammatory and coagulation responses. Protease-activated receptor 1 (PAR1), an important regulator of endothelial barrier function and blood coagulation, has been proposed to be involved in the lethal sequelae of sepsis, but it is unknown whether activation of PAR1 is beneficial or harmful. Using a cell-penetrating peptide (pepducin) approach, we provide evidence that PAR1 switched from being a vascular-disruptive receptor to a vascular-protective receptor during the progression of sepsis in mice. Unexpectedly, we found that the protective effects of PAR1 required transactivation of PAR2 signaling pathways. Our results suggest therapeutics that selectively activate PAR1-PAR2 complexes may be beneficial in the treatment of sepsis. 相似文献
48.
Anika L. Hines Debra Roter Bri K. Ghods Dinoso Kathryn A. Carson Gail L. Daumit Lisa A. Cooper 《Patient education and counseling》2018,101(2):233-240
Objective
We examined the prevalence and extent of informed decision-making (IDM) and patient-centered decision-making (PCDM) in primary care visits of African Americans with depression.Methods
We performed a cross-sectional analysis of audiotaped clinical encounters and post-visit surveys of 76 patients and their clinicians. We used RIAS to characterize patient-centeredness of visit dialogue. IDM entailed discussion of 3 components: the nature of the decision, alternatives, and pros/cons. PCDM entailed discussion of: lifestyle/coping strategies, knowledge/beliefs, or treatment concerns. We examined the association of IDM and PCDM with visit duration, overall patient-centeredness, and patient/clinician interpersonal ratings.Results
Approximately one-quarter of medication and counseling decisions included essential IDM elements and 40% included at least one PCDM element. In high patient-centered visits, IDM was associated with patients feeling respected in counseling and liking clinicians in medication decisions. IDM was not related to clinician ratings. In low patient-centered visits, PCDM in counseling decisions was positively associated with patients feeling respected and clinicians respecting patients.Conclusions
The associations between IDM and PCDM with interpersonal ratings was moderated by overall patient-centeredness of the visit, which may be indicative of broader cross-cultural communication issues.Practice implications
Strengthening partnerships between depressed African Americans and their clinicians may improve patient-engaged decision-making. 相似文献49.
Katina Schinnerling Anika Geelhaar-Karsch Kristina Allers Julian Friebel Kristina Conrad Christoph Loddenkemper Anja A. Kühl Ulrike Erben Ralf Ignatius Verena Moos Thomas Schneider 《Infection and immunity》2015,83(2):482-491
Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple''s disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11chigh myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN+ DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium. 相似文献
50.