全文获取类型
收费全文 | 5124篇 |
免费 | 23篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 736篇 |
妇产科学 | 208篇 |
基础医学 | 546篇 |
口腔科学 | 197篇 |
临床医学 | 165篇 |
内科学 | 1060篇 |
皮肤病学 | 207篇 |
神经病学 | 302篇 |
特种医学 | 86篇 |
外科学 | 1151篇 |
综合类 | 16篇 |
预防医学 | 96篇 |
眼科学 | 84篇 |
药学 | 156篇 |
中国医学 | 2篇 |
肿瘤学 | 122篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 92篇 |
2020年 | 12篇 |
2019年 | 620篇 |
2018年 | 513篇 |
2017年 | 316篇 |
2016年 | 14篇 |
2015年 | 13篇 |
2014年 | 26篇 |
2013年 | 43篇 |
2012年 | 24篇 |
2011年 | 25篇 |
2010年 | 25篇 |
2009年 | 14篇 |
2008年 | 18篇 |
2007年 | 12篇 |
2006年 | 15篇 |
2005年 | 10篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1987年 | 1篇 |
1985年 | 264篇 |
1984年 | 354篇 |
1983年 | 198篇 |
1982年 | 286篇 |
1981年 | 280篇 |
1980年 | 259篇 |
1979年 | 299篇 |
1978年 | 240篇 |
1977年 | 218篇 |
1976年 | 252篇 |
1975年 | 221篇 |
1974年 | 194篇 |
1973年 | 211篇 |
1972年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有5157条查询结果,搜索用时 15 毫秒
1.
2.
Conall T. Morgan Brigitte Mueller Varsha Thakur Vitor Guerra Callaghan Jull Luc Mertens Mark Friedberg Fraser Golding Mike Seed Steven E.S. Miner Edgar T. Jaeggi Cedric Manlhiot Lynne E. Nield 《The Canadian journal of cardiology》2019,35(4):453-461
Background
The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.Methods
A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves.Results
Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention.Conclusions
In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler. 相似文献3.
4.
5.
6.
7.
The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing. 相似文献
8.
Dr. Elina Ikonen Armi Salo Mirja Somer Hannu Somer Leena Pääkkönen Leena Peltonen 《American journal of medical genetics. Part A》1992,43(4):753-758
A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc. 相似文献
9.
Sanjay Varikuti Chaitenya Verma Gayathri Natarajan Steve Oghumu Abhay R. Satoskar 《The American journal of pathology》2021,191(5):809-816
Interferon (IFN)-γ is indispensable in the resolution of cutaneous leishmaniasis (CL), while the Th2 cytokines IL-4, IL-10, and IL-13 mediate susceptibility. A recent study found that miR155, which promotes CD4+ Th1 response and IFN-γ production, is dispensable in the control of Leishmania donovani infection. Here, the role of miR155 in CL caused by L. major was investigated using miR155-deficient (miR155−/−) mice. Infection was controlled significantly quicker in the miR155−/− mice than in their wild-type (WT) counterparts, indicating that miR155 contributes to the pathogenesis of CL. Faster resolution of infection in miR155−/− mice was associated with increased levels of Th1-associated IL-12 and IFN-γ and reduced production of Th2- associated IL-4, IL-10, and IL-13. Concentrations of IFN-γ+CD8+ T cells and natural killer cells in draining lymph nodes were significantly higher in the L. major−infected miR155−/− mice than in the infected WT mice, as indicated by flow-cytometry. After in vitro IFN-γ stimulation, nitric oxide and IL-12 production were increased, IL-10 production was decreased, and parasite clearance was enhanced in L. major−infected miR155−/− DCs compared to those in WT DCs. Furthermore, IFN-γ production from activated miR155−/− T cells was significantly enhanced in L. major−infected miR155−/− DCs. Together, these findings demonstrate that miR155 promotes susceptibility to CL caused by L. major by promoting Th2 response and inhibiting DC function.Leishmania are obligate intracellular protozoans that infect phagocytes and cause a spectrum of clinical diseases such as cutaneous leishmaniasis (CL) and visceral leishmaniasis. Common in the tropical and subtropical regions, leishmaniasis affects over 1 billion people worldwide, with an incidence of up to 1 million cases per year.1 CL is the most common type of Leishmania infection, manifesting as localized skin lesions that can become chronic, leading to significant tissue destruction and disfigurement.2,3 It is well documented that the induction of a Th1 response and interferon (IFN)-γ are indispensable in the resolution of CL caused by Leishmania major,4 whereas disease progression is associated with the induction of a Th2 response and the production of cytokines such as IL-4 and IL-10.5 Establishing a disease-resolving response in the host is largely dependent on the ability to mount an appropriate Th1 immune response.4 Crucial in this response is the stimulation and activation of DCs that direct T-cell proliferation and differentiation toward IFN-γ–producing Th1 cells.6,7 In addition to activating of phagocytic cells, IFN-γ induces the production of reactive nitrogen species, specifically nitric oxide (NO), leading to enhanced parasite clearance.4miR155 is a recognized regulator of immune cell function and immune response. miR155 enhances macrophage and DC activation and induces inflammatory response,8,9 and up-regulation of miR155 in CD4+ T cells promotes preferential Th1 differentiation and IFN-γ production10 by suppressing the expression of suppressor of cytokine signaling (SOCS)-1.11, 12, 13, 14 Conversely, miR155 gene–deficient mice exhibit diminished levels of Th1/Th17 cells, macrophages, and DCs.15 miR155 has also been shown to play a role in regulating effector Th2 response.16, 17, 18 Collectively, these findings suggest that miR155 regulates both Th1 and Th2 responses, which control the outcome of CL caused by L. major. Therefore, the role of miR155 in immunity to L. major using miR155−/− mice was investigated in the present study. The findings show that miR155 is not required for the induction of a Th1 response and IFN-γ in L. major infection. Rather, miR155 plays a disease-exacerbating role in CL by attenuating DC function and Th1 response and promoting Th2 response. 相似文献
10.
Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length 总被引:8,自引:0,他引:8
下载免费PDF全文
![点击此处可从《Journal of medical genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Age of onset (AO) of Huntington disease (HD) is known to be correlated with the length of an expanded CAG repeat in the HD gene. Apolipoprotein E (APOE) genotype, in turn, is known to influence AO in Alzheimer disease, rendering the APOE gene a likely candidate to affect AO in other neurological diseases too. We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length. Genotyping for APOE was performed blind to clinical information. In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients, we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females. Such a sex difference in AO was not apparent for any of the other APOE genotypes. Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO. 相似文献