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   254389篇
  免费   25149篇
  国内免费   19967篇
耳鼻咽喉   1999篇
儿科学   2268篇
妇产科学   2994篇
基础医学   32227篇
口腔科学   4259篇
临床医学   36114篇
内科学   35529篇
皮肤病学   2380篇
神经病学   14447篇
特种医学   9479篇
外国民族医学   198篇
外科学   24329篇
综合类   43625篇
现状与发展   74篇
一般理论   27篇
预防医学   15101篇
眼科学   8067篇
药学   27735篇
  290篇
中国医学   15545篇
肿瘤学   22818篇
  2024年   274篇
  2023年   3864篇
  2022年   6134篇
  2021年   12040篇
  2020年   10560篇
  2019年   9213篇
  2018年   9655篇
  2017年   8504篇
  2016年   8086篇
  2015年   12159篇
  2014年   14937篇
  2013年   12519篇
  2012年   18715篇
  2011年   21526篇
  2010年   13022篇
  2009年   10063篇
  2008年   13331篇
  2007年   13380篇
  2006年   13588篇
  2005年   13844篇
  2004年   8195篇
  2003年   7606篇
  2002年   6361篇
  2001年   5664篇
  2000年   6404篇
  1999年   7138篇
  1998年   4652篇
  1997年   4680篇
  1996年   3621篇
  1995年   3513篇
  1994年   2896篇
  1993年   1970篇
  1992年   2216篇
  1991年   1848篇
  1990年   1567篇
  1989年   1335篇
  1988年   1136篇
  1987年   955篇
  1986年   737篇
  1985年   611篇
  1984年   349篇
  1983年   216篇
  1982年   118篇
  1981年   126篇
  1980年   83篇
  1979年   91篇
  1977年   1篇
  1965年   1篇
  1962年   1篇
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1 (CCPG1) is involved in the corneal antifungal immune response. METHODS: Human corneal epithelial cells (HCECs) and human myeloid leukemia mononuclear cells (THP-1) macrophages stimulated by Aspergillus fumigatus (A. fumigatus) were used as cell models. The expression of CCPG1 mRNA was detected by qRT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β (IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1 (CLEC-1) in THP-1 macrophages. RESULTS: The expression of CCPG1 started to increase at 4h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages. CONCLUSION: As a specific autophagy protein of non-canonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.  相似文献   
992.
993.
994.
995.
996.

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Objective

To seek a potential therapeutic target in glutamine-addicted ccRCC.

Design, setting, and participants

Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells.

Outcome measurements and statistical analysis

Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses.

Results and limitations

We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR] = 2.04, cancer-specific survival [CSS] HR = 2.95; all p < 0.001) and Shanghai (OS HR = 2.07, CSS HR = 3.92; all p < 0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor β expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells.

Conclusions

Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC.

Patient summary

In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23–high patients had significantly poorer survival than IL-23–low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors.  相似文献   
997.

Background and purpose

It is not conclusive that magnetic resonance (MR)-based carotid atherosclerotic plaque assessment identifies high-risk features associated with cerebrovascular events. We aimed to systematically summarize the association of MR imaging (MRI)-determined intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thinning/rupture of the fibrous cap (TRFC) with subsequent ischemic events.

Materials and methods

We performed a comprehensive literature search evaluating the association of MRI-based carotid plaque composition with ischemic outcomes. We included cohort studies examining IPH, LRNC, or TRFC with mean follow-up of  6 months and an outcome measure of ipsilateral ischemic events. A meta-analysis was done according to the Cochrane guideline.

Results

We identified 13 studies including 1.150 patients and 1.208 analyzed carotid arteries, with mean follow-up of 21.1 months. The hazard ratios (HR) for IPH, LRNC, and TRFC as predictors of subsequent ischemic events were 4.41 (95% CI: 2.87, 6.79), 3.00 (95% CI: 1.51, 5.95), and 5.94 (95% CI: 2.66, 13.28), respectively. The predictive value of carotid plaque MRI for ischemic events was acceptable, with sensitivity of 0.80 (95% CI: 0.66, 0.90) and specificity of 0.63 (95% CI: 0.57, 0.68). However, it was limited to confirm or exclude future ischemic events in clinical context, with positive likelihood ratio (LR) of 2.2 (95% CI: 1.9, 2.5) and negative LR of 0.31 (95% CI: 0.18, 0.55). No statistically significant heterogeneity or publication bias was observed.

Conclusion

The presence of IPH, LRNC, and TRFC determined by MRI is associated with increased risk of future ischemic events, but its predictive value is moderate and should not be used for confirmation or exclusion of future ischemic events in clinical context.  相似文献   
998.

Background and purpose

Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs.

Materials and methods

A retrospective review of CTA neck studies in all adult patients presenting to our institution during the 19-month study interval was performed to determine the presence of carotid webs. Subsequent chart review of these patients with webs was performed to assess their clinical history and to obtain demographic detail.

Results

A total of 14 patients were identified with carotid webs in the study population. The mean age of patients with webs was 42.1?years (range: 28–54), consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web patients had a history of ischemic stroke, each ipsilateral to the side of web, and at least four of these patients had recurrent ischemic stroke.

Conclusion

We provide one of the largest sample sizes of webs gathered in a single study. Given its association with ischemic stroke, carotid webs should be assessed for in all patients presenting with ischemic stroke, especially younger African Americans.  相似文献   
999.

Objectives

Using finite element analysis and biomechanical tests, the biomechanical behaviors of Medial Sustainable Nail (MSN) and Proximal Femoral Nail Antirotation (PFNA) were compared for the fixation of fracture type of AO/OTA 31-A2.3.

Methods

Finite element software Abaqus 6.14 was used to conduct axial loading of 2100?N and we analyzed the von Mises stress distribution and the model displacement of two implant models. Biomechanical tests were separately conducted in the axial stiffness test and axial cyclical loading test on a mechanical testing machine.

Results

The results indicate that von Mises stress of MSN was lower than that of PFNA, and the model displacement in the MSN group was lower than that in the PFNA group. In the axial stiffness tests, MSN group was stiffer than PFNA construct. With respect to the axial load to ultimate failure, the PFNA construct exhibited higher loads exceeding 4000?N while the MSN construct withstood 3313.8?±?92.8?N. Specifically, F10mm was 2178.6?±?133.2?N of the MSN group and 1822.6?±?93.1?N of the PFNA group (P?=?0.001). Additionally, X2100N was 9.8?±?0.5?mm of the MSN group and 11.7?±?0.7?mm of the PFNA group (P?=?0.002). The MSN group exhibited superior performances in terms of the mean value of the vertical displacement, frontal rotation angle, and lateral rotation angle.

Conclusions

The results indicated that the MSN construct might exhibit a better biomechanical performance when compared with that of the PFNA in reducing displacement and anti-varus in fracture type of AO/OTA 31-A2.3.  相似文献   
1000.
Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults, and study its effect on the the prevention of calcium oxalate kidney stones. Methods OxF was screened and cultured from fresh feces of healthy adults. The rat model of calcium oxalate stone was established by esophageal gavage of 0.8% of ethylene glycol. Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table. Three groups were treated with 106 CFU, 107 CFU, 108 CFU viable OxF every day, respectively, for 4 weeks. The blood and 24-hour urine samples were collected to detect the serum creatinine, urea nitrogen, serum and urine calcium, phosphorus, magnesium and urine oxalate every week. At the end of the 4th week, the rats were sacrificed and the kidney tissues were stained with HE and Yasue. The deposition and content of calcium oxalate crystals were observed under a light microscope. Results The bacteria strain isolated from fresh feces of healthy adults was 100% as same as the known ATCC35274 bacteria strain, which means the strain screened is OxF. Among the 5 groups, there were no significant differences in body weight, Scr, BUN, serum calcium, blood magnesium, blood phosphorus, urinary magnesium and urinary phosphorus. The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P<0.05). After intervention with OxF solution, the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P<0.05), while there was no significant difference between the other intervention groups and the model. The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model, but the difference did not reach statistical significance (P>0.05). The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P<0.05), and continued to decrease for the next 3 weeks. After 4 weeks of intervention, no crystal formation was observed in the control group under the deflection microscope, but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla. The crystals were piled up and connected to each other. Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys. Compared with the model, there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group, while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P<0.05). Conclusions OxF are successively screened from healthy adults. Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion, prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats.  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