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   24423篇
  免费   1337篇
  国内免费   485篇
耳鼻咽喉   157篇
儿科学   128篇
妇产科学   423篇
基础医学   2078篇
口腔科学   715篇
临床医学   1945篇
内科学   2484篇
皮肤病学   316篇
神经病学   561篇
特种医学   464篇
外国民族医学   292篇
外科学   1517篇
综合类   5698篇
预防医学   2346篇
眼科学   235篇
药学   3283篇
中国医学   1963篇
肿瘤学   1640篇
  2024年   7篇
  2023年   41篇
  2022年   111篇
  2021年   217篇
  2020年   209篇
  2019年   193篇
  2018年   344篇
  2017年   234篇
  2016年   279篇
  2015年   361篇
  2014年   4296篇
  2013年   3177篇
  2012年   2605篇
  2011年   2322篇
  2010年   3688篇
  2009年   3387篇
  2008年   1597篇
  2007年   714篇
  2006年   546篇
  2005年   444篇
  2004年   371篇
  2003年   299篇
  2002年   205篇
  2001年   142篇
  2000年   95篇
  1999年   67篇
  1998年   49篇
  1997年   37篇
  1996年   35篇
  1995年   15篇
  1994年   24篇
  1993年   23篇
  1992年   18篇
  1991年   8篇
  1990年   6篇
  1989年   4篇
  1988年   6篇
  1987年   11篇
  1986年   7篇
  1985年   6篇
  1984年   6篇
  1983年   4篇
  1982年   3篇
  1981年   5篇
  1980年   6篇
  1979年   2篇
  1978年   4篇
  1977年   4篇
  1973年   3篇
  1971年   4篇
排序方式: 共有10000条查询结果,搜索用时 421 毫秒
1.
目的 分析10-MDP-钙盐形成对牙本质粘接成绩的影响。方法 采用酸蚀冲洗粘接模式,根据牙本质表面的处理方式和选择粘接剂的不同将牙齿随机分为以下4组(n=5)进行处理,制作牙本质/树脂粘接试件:①对照组,直接使用全酸蚀粘接剂Single bond 2(SB2)处理后粘接;②10-MDP组,使用SB2处理进行粘接前,牙本质表面以含有磷酸酯单体10-MDP的自配底涂剂预处理;③CHX组,使用SB2处理进行粘接前,先以氯己定(CHX)预处理牙本质表面;④SBU组,使用包含10-MDP的通用型粘接剂Single bond universal(SBU)处理后进行粘接。通过微拉伸测试(μTBS)测试粘接强度,以X射线衍射(XRD)、原位酶谱测试表征自配10-MDP底涂剂和两种牙本质粘接剂处理的牙本质表面,分析10-MDP-钙盐形成对牙本质粘接成绩的影响。结果 微拉伸结果显示,不同处理方式的粘接试件在24 h水储后没有表现出明显的统计学差异(P>0.1);经过6个月的水储后,与10-MDP组和SBU组相比,对照组的微拉伸强度显著降低(P<0.05),而CHX组的微拉伸强度没有明显变化(P>0.05)。XRD结果显示,在10-MDP组和SBU组均检测到10-MDP-钙盐形成的特征性峰,表明有10-MDP-钙盐的形成。原位酶谱结果显示,10-MDP组与SBU组之间混合层荧光强度没有明显区别,但均明显高于对照组,CHX组荧光强度低于10-MDP组与SBU组。结论 10-MDP-钙盐的形成能够保护暴露的胶原纤维不接触到MMPs而免于水解,从而增强牙本质/树脂的粘接成绩。  相似文献   
2.
3.
Objective: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute.

Methods: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR?=?0.813, 95%CI?=?0.694–0.953, p?=?0.010) in overall populations.

Conclusions: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.  相似文献   
4.
目的:分析超声内镜引导下经支气管针吸活检(endobronchial ultrasound-guided transbronchial needle aspiration,EBUS-TBNA)术中肿大纵隔淋巴结的超声图像特点,探讨EBUS-TBNA超声内镜对纵隔淋巴结良恶性的鉴别诊断价值,以期提高EBUS-TBNA对纵隔淋巴结恶性病变的活检率。方法:回顾性分析2014年10月至2018年11月行EBUS-TBNA患者的超声内镜图像。我们使用以下EBUS超声内镜特征来预测淋巴结的良恶:回声,长轴长度,短轴长度,纵横比,形态,边界,淋巴门有无,淋巴结内血流信号分级。将超声检查结果与最终病理结果或临床随访结果进行比较。采用SPSS 20.0软件进行统计学分析,采用logistic回归分析评价肿大淋巴结EBUS-TBNA超声内镜下的特征与良恶性的相关性,以 P<0.05 为标准判定差异有统计学意义。结果:对130例纵隔淋巴结肿大患者的227个淋巴结进行回顾性分析,67.4%的肿大淋巴结被证实为恶性转移。Logistic回归分析显示回声、长轴及短轴的长度、正常淋巴门结构的消失是诊断恶性淋巴结的独立预测因素。结论:纵隔恶性淋巴结具有一定的超声特征,可以通过这些超声特征提高EBUS-TBNA对纵隔恶性淋巴结的检出率。  相似文献   
5.
Using JEG-3 and BeWo cells, we examined the effect of “real life” mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal and hormone-stimulated matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) protein expression was evaluated. Under basal conditions, the PAH mixtures increased hCG and decreased hPLGF levels in both cell lines, while hPL expression was stimulated in JEG-3 and inhibited in BeWo. There was no effect on the MMP-2/MMP-9 ratio or VEGF expression. In hormone-stimulated cells, PAH mixtures changed the MMP-2/MMP-9 ratio in JEG-3 cells in favor of MMP-9, while in BeWo MMP-2 was favored. The effect on VEGF expression was cell specific and dependent on the mixture. In hCG-treated cells, only Mix II inhibited VEGF expression in JEG-3 cells. Neither PAH mixtures affected this protein in BeWo cells. In hPL-treated cells, Mix I had a stimulatory effect in JEG-3 cells, while Mix II exerted an inhibitory effect in BeWo cells. In hPLGF-treated cells, Mix II decreased in JEG-3 cells, but in BeWo cells, both mixtures increased VEGF expression. Considering that the evaluated protein hormones play crucial roles in angiogenesis and neovascularization in the placenta, “real life” PAH mixtures by disrupting protein hormones levels, the MMP-2/MMP-9 ratio and VEGF expression can lead to insufficiency and many pregnancy-related disorders.  相似文献   
6.
Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.  相似文献   
7.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
8.
BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.  相似文献   
9.
The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.  相似文献   
10.
Summary The quantity of protein and carbohydrate comprising the matrix of calcium oxalate monohydrate (COM) renal stones was found to decrease with distance from the surface of the stone. The average organic concentration of stones 3 to 30 mm in diameter ranged from 5.7% at the surface to 2.7% at the core. This concentration gradient suggests matrix involvement in a “growth front” on stone surfaces with migration of organic material from the “older” interior. The matrix distribution was not readily correlated with density variations or with the presence of hydroxyapatite or calcium oxalate dihydrate. Surface matrix concentrations were greater than amounts predicted by physical adsorption. Electron microscopy confirmed the presence of the organic-rich surface layer and also suggested that increase in stone size occurs predominantly by crystal growth with microcrystal aggregates as growth centers.  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