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   4715篇
  免费   313篇
  国内免费   27篇
耳鼻咽喉   38篇
儿科学   101篇
妇产科学   84篇
基础医学   830篇
口腔科学   124篇
临床医学   283篇
内科学   1095篇
皮肤病学   135篇
神经病学   455篇
特种医学   112篇
外科学   660篇
综合类   30篇
一般理论   3篇
预防医学   255篇
眼科学   115篇
药学   343篇
中国医学   11篇
肿瘤学   381篇
  2023年   44篇
  2022年   103篇
  2021年   187篇
  2020年   110篇
  2019年   133篇
  2018年   160篇
  2017年   117篇
  2016年   111篇
  2015年   157篇
  2014年   176篇
  2013年   198篇
  2012年   309篇
  2011年   307篇
  2010年   191篇
  2009年   157篇
  2008年   283篇
  2007年   251篇
  2006年   262篇
  2005年   272篇
  2004年   230篇
  2003年   218篇
  2002年   188篇
  2001年   76篇
  2000年   69篇
  1999年   80篇
  1998年   43篇
  1997年   34篇
  1996年   21篇
  1995年   23篇
  1994年   15篇
  1993年   10篇
  1992年   41篇
  1991年   40篇
  1990年   32篇
  1989年   40篇
  1988年   29篇
  1987年   35篇
  1986年   39篇
  1985年   27篇
  1984年   19篇
  1983年   23篇
  1982年   10篇
  1981年   12篇
  1979年   23篇
  1978年   13篇
  1973年   12篇
  1971年   12篇
  1970年   14篇
  1969年   12篇
  1968年   9篇
排序方式: 共有5055条查询结果,搜索用时 31 毫秒
1.
2.
Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.  相似文献   
3.
BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.  相似文献   
4.
In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.  相似文献   
5.
6.
OBJECTIVE: Continuous retrograde cerebral perfusion during aortic arch surgery is associated with cerebral edema. In this report, we describe the clinical use of a new type of intermittent retrograde cerebral perfusion. SUBJECTS AND METHODS: Fourteen patients with a Stanford type A dissection were included in this study. With the usual method of retrograde cerebral perfusion, about 2,500 mL venous blood is drained from bicaval cannulae into a hard-shell reservoir, and oxygenated blood is perfused through the superior vena caval cannula. The flow rate is 300 mL/min. After about 15 min, retrograde perfusion is discontinued, and drainage from the bicaval cannulae is restarted. When a bloodless field is necessary, perfusion also is discontinued. RESULTS: Two to seven cycles of intermittent retrograde cerebral perfusion were administered (average, 3.1+/-0.4, mean+/-SD). The total retrograde perfusion time was 36.0+/-1.9 min which was equivalent to 74.8% of the circulatory arrest time. No patient developed edema of the upper body. The time to wake-up was 3 to 14 h (average, 6.5+/-1.0 h). No patient suffered any neurologic complications even though the time of circulatory arrest was greater than 60 min in four cases. Head magnetic resonance imaging or computed tomography was performed in 12 cases, and no evidence of hypoxic brain injury was detected. CONCLUSIONS: Our clinical experience using a moderate amount of intermittent retrograde cerebral perfusion is superior to continuous retrograde cerebral perfusion for protecting the brain during aortic arch surgery.  相似文献   
7.
Thirty-five patients with benign prostatic hyperplasia (age range: 45-88 years; average: 67.5 years) underwent local thermotherapy with prostathermer. Clinical therapeutic effect was evaluated in 30 of the 35 patients: 2 patients interrupting from therapy and 3 receiving pretherapeutic indwelling catheters were not included. A total of 6 treatments (2 per week) were performed, each lasting for 60 minutes. As for subjective improvement, improvement of nocturia was noted in 70.0% of all patients and sense of residual urine in 70.7%. Post-therapeutic nocturnal and daytime decreases in urination frequency were statistically significant (p less than 0.01). Objective improvement in residual urine volume occurred in 19 of the 30 cases, and elevation in uroflowmetric maximal flow rate following therapy was statistically significant (p less than 0.05). Among complications ascribable to catheter insertion were urethral bleeding (3 cases), epididymitis (1 case) and pyuria (1 case). Therapeutic result based primarily on subjective symptoms and partly on objective findings was fairly good in 17 cases (about 57%), and slightly good in 25 cases (about 83%). In conclusion, this therapy seems to be useful in the treatment of benign prostatic hyperplasia.  相似文献   
8.
To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development.  相似文献   
9.
To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo.  相似文献   
10.
We report a patient who developed overlapping symptoms of ophthalmoplegia and oropharyngeal palsy after Campylobacter jejuni infection. A 15-year-old man had diarrhea and fever, and developed dysarthria, diplopia and ptosis two weeks later. He did not show ataxia, weakness or abnormal tendon reflexes in the extremities during the clinical course. In the acute phase of the disease, we found significant elevation of anti-GQlb and anti-GTla IgG antibodies in the serum, and high-dose intravenous immunoglobulin therapy remarkably ameliorated the symptoms. Our patient was atypical of Fisher syndrome or pharyngeal-cervical-brachial (PCB) weakness, and this is the first case of multiple cranial neuropathy associated with C. jejuni infection.  相似文献   
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