首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   191篇
  免费   11篇
耳鼻咽喉   2篇
儿科学   7篇
妇产科学   1篇
基础医学   33篇
口腔科学   2篇
临床医学   11篇
内科学   58篇
皮肤病学   8篇
神经病学   18篇
外科学   20篇
预防医学   6篇
眼科学   1篇
药学   9篇
肿瘤学   26篇
  2022年   2篇
  2021年   8篇
  2020年   4篇
  2019年   7篇
  2018年   6篇
  2017年   9篇
  2016年   3篇
  2015年   6篇
  2014年   8篇
  2013年   12篇
  2012年   10篇
  2011年   12篇
  2010年   15篇
  2009年   7篇
  2008年   9篇
  2007年   9篇
  2006年   4篇
  2005年   4篇
  2004年   6篇
  2003年   2篇
  2002年   8篇
  2001年   3篇
  2000年   9篇
  1999年   3篇
  1998年   4篇
  1997年   2篇
  1995年   2篇
  1993年   1篇
  1992年   6篇
  1991年   4篇
  1990年   3篇
  1989年   3篇
  1987年   2篇
  1986年   2篇
  1985年   1篇
  1984年   1篇
  1983年   1篇
  1980年   1篇
  1978年   1篇
  1968年   1篇
  1967年   1篇
排序方式: 共有202条查询结果,搜索用时 31 毫秒
131.
AT‐rich interactive domain‐containing protein 1A (ARID1A) loss‐of‐function mutation accompanied by a loss of ARID1A protein expression is frequently observed in endometrial carcinomas. However, the molecular mechanisms linking these genetic changes to the altered pathways regulating tumour initiation, maintenance and/or progression remain poorly understood. Thus, the main aim of this study was to analyse the role of ARID1A loss of function in endometrial tumorigenesis. Here, using different endometrial in vitro and in vivo models, such as tumoral cell lines, 3D primary cultures and metastatic or genetically modified mouse models, we show that altered expression of ARID1A is not enough to initiate endometrial tumorigenesis. However, in an established endometrial cancer context, ARID1A loss of function accelerates tumoral progression and metastasis through the disruption of the G2/M cell cycle checkpoint and ATM/ATR‐mediated DNA damage checkpoints, increases epithelial cell proliferation rates and induces epithelial mesenchymal transition through the activation of histone deacetylase 6 (HDAC6). Next, we demonstrated that the inhibition of HDAC6 function, using the HDAC6‐specific inhibitor ACY1215 or by transfection with HDAC6 short hairpin RNA (shRNA), can reverse the migratory and invasive phenotype of ARID1A‐knockdown cells. Further, we also show that inhibition of HDAC6 activity causes an apoptotic vulnerability to etoposide treatments in ARID1A‐deficient cells. In summary, the findings exposed in this work indicate that the inhibition of HDAC6 activity is a potential therapeutic strategy for patients suffering from ARID1A‐mutant endometrial cancer diagnosed in advanced stages.  相似文献   
132.
OjectiveThe objective of the study is to determine the frequency and the clinical significance of autoantibodies to the pericentromeric heterochromatin protein 1 (HP1). So far this antinuclear antibody specificity has been mainly reported in patients with the CREST syndrome.MethodsWe screened the sera of 199 individuals, including patients suffering from various autoimmune disorders (Group I, n = 145) and non autoimmune diseases (Group II, n = 44 patients) as well as healthy individuals (Group III, n = 30). The sera were systematically tested by Western blot and ELISA using a GST–HP1α fusion protein as an antigen.ResultsAnti-HP1 antibodies were detected in 32% of patients in Group I, 11.3% in Group II and 3.3% of individuals in Group III. They could be detected in sera containing or not antinuclear antibodies detectable by indirect immunofluorescence. Anti-HP1 antibodies were mostly associated with the CREST and Sjogren's syndromes (70% and 44.4%, respectively). They could also be detected in 22.2% of patients suffering from various other autoimmune diseases. However, their negative predictive value was 94% in the CREST syndrome.ConclusionAnti-HP1 autoantibodies are associated with a large spectrum of disorders. However, they have a diagnostic value in the CREST syndrome.  相似文献   
133.
134.

Context  

Severe sepsis is associated with high mortality and increased costs. The ‘Surviving Sepsis Campaign’ (SSC) protocol was developed as an international initiative to reduce mortality. However, its cost-effectiveness is unknown.  相似文献   
135.
136.
The midbrain periaqueductal gray is a key structure for the mediation of an integrated defence behaviour. Although a prominent role for glutamate in PAG mechanisms is supported by both behavioural and morphological studies, whether PAG afferents conveying somatosensory information constitute a source of glutamatergic input to the PAG remains unknown. Here, we have compared the projection pattern of orthogradely-labelled spinoannular fibres with the distribution of glutamate-like immunoreactivity in the PAG at the light microscopic level. Transaxonal labelling was observed throughout the whole rostrocaudal axis of the PAG except for the dorsolateral regions. Cell-processes and terminal-reminiscent puncta were strongly immunoreactive in all PAG regions, including the dorsolateral areas. To ascertain whether glutamate-immunoreactive puncta observed at light microscopy indeed constituted axon terminals of the spinoannular system, glutamate-like immunoreactivity was assessed in orthogradely-labelled synaptic terminals using a post-embedding immunogold procedure for electron microscopy. Quantitative analysis of gold particle densities revealed over twice as strong an immunoreactivity in anatomically-identified spinoannular axon terminals as in dendrites postsynaptic to them, perikarya and inhibitory Gray II synapses, as well as an over 5-fold heavier immunolabelling than in glial profiles. These findings reveal that glutamate is accumulated in synaptic terminals of the spinoannular system, supporting a neurotransmitter role for this acidic amino acid in spinofugal afferents to the PAG.  相似文献   
137.
Anisakis, anisakidosis, and allergy to Anisakis   总被引:2,自引:1,他引:1  
E. Buendia 《Allergy》1997,52(5):481-482
  相似文献   
138.
We report our experience in radiofrequency catheter ablation between April, 1992 and December, 1998, in which we treated 287 patients less than 18 years of age (mean 14.3 +/- 3.1 years) with supraventricular tachycardia. Accessory, pathways were the arrhythmic substrate in 252 of the patients (87.8%), the patients having a total of 265 accessory pathways. Atrioventricular nodal re-entry was the cause of tachycardia in 26 patients (9.0%), while atrial flutter was detected in the remaining 9 patients (3.1%). We were able successfully to eliminate the accessory pathway in 236 patients (89%), but 25 patients had recurrent arrhythmias. Ablation proved successful in all cases of atrioventricular node re-entry tachycardia, the slow pathway being ablated in 25 patients, and the fast pathway in only one case. Recurrence of the arrhythmia occurred in three patients (11.5%). We performed a second ablation in these children, all then proving successful. The ablation was successful in all cases of atrial flutter, with one recurrence (11.1%). Overall, therefore, ablation was immediately successful in 271 patients (94.4%), with a recurrence of the arrhythmia in 29 cases (10.7%). The incidence of serious complications was 2.09%. There was one late death due to infective endocarditis, 3 patients suffered complete heart block, 1 had mild mitral regurgitation, and 1 patient developed an haematoma in the groin. We conclude that radiofrequency catheter ablation can now be considered a standard option for the management of paroxysmal supraventricular tachycardias in children and young adults.  相似文献   
139.
140.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号