全文获取类型
收费全文 | 21656篇 |
免费 | 1608篇 |
国内免费 | 799篇 |
专业分类
耳鼻咽喉 | 305篇 |
儿科学 | 307篇 |
妇产科学 | 473篇 |
基础医学 | 2567篇 |
口腔科学 | 259篇 |
临床医学 | 2029篇 |
内科学 | 2714篇 |
皮肤病学 | 214篇 |
神经病学 | 712篇 |
特种医学 | 954篇 |
外科学 | 2298篇 |
综合类 | 3553篇 |
预防医学 | 1021篇 |
眼科学 | 104篇 |
药学 | 1750篇 |
5篇 | |
中国医学 | 674篇 |
肿瘤学 | 4124篇 |
出版年
2024年 | 25篇 |
2023年 | 231篇 |
2022年 | 586篇 |
2021年 | 730篇 |
2020年 | 682篇 |
2019年 | 461篇 |
2018年 | 493篇 |
2017年 | 599篇 |
2016年 | 672篇 |
2015年 | 703篇 |
2014年 | 1423篇 |
2013年 | 1332篇 |
2012年 | 1423篇 |
2011年 | 1549篇 |
2010年 | 1281篇 |
2009年 | 1236篇 |
2008年 | 1276篇 |
2007年 | 1253篇 |
2006年 | 1103篇 |
2005年 | 961篇 |
2004年 | 821篇 |
2003年 | 720篇 |
2002年 | 573篇 |
2001年 | 607篇 |
2000年 | 463篇 |
1999年 | 451篇 |
1998年 | 336篇 |
1997年 | 331篇 |
1996年 | 277篇 |
1995年 | 267篇 |
1994年 | 225篇 |
1993年 | 127篇 |
1992年 | 107篇 |
1991年 | 81篇 |
1990年 | 100篇 |
1989年 | 64篇 |
1988年 | 59篇 |
1987年 | 45篇 |
1986年 | 29篇 |
1985年 | 53篇 |
1984年 | 65篇 |
1983年 | 34篇 |
1982年 | 30篇 |
1981年 | 31篇 |
1980年 | 37篇 |
1979年 | 42篇 |
1978年 | 20篇 |
1977年 | 11篇 |
1976年 | 11篇 |
1973年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 218 毫秒
11.
《Zeitschrift für medizinische Physik》2022,32(2):143-148
BackgroundIt is shown that tumour volume distributions can yield information on two aspects of cancer research: tumour induction and tumour control.Materials and methodsFrom the hypothesis that the intrinsic distribution of breast cancer volumes follows an exponential distribution, firstly the probability density function of tumour growth time was deduced via a mathematical transformation of the probability density functions of tumour volumes. In a second step, the distribution of tumour volumes was used to model the variation of the clonogenic cell number between patients in order to determine tumour control probabilities for radiotherapy patients.ResultsDistribution of lag times, i.e. the time from the appearance of the first fully malignant cell until a clinically observable cancer, can be used to deduce the probability of tumour induction as a function of patient age. The integration of the volume variation with a Poisson-TCP model results in a logistic function which explains population-averaged survival data of radiotherapy patients.ConclusionsThe inclusion of tumour volume distributions into the TCP formalism enables a direct link to be deduced between a cohort TCP model (logistic) and a TCP model for individual patients (Poisson). The TCP model can be applied to non-uniform tumour dose distributions. 相似文献
12.
《Journal of thoracic oncology》2021,16(10):1694-1704
IntroductionIn patients with NSCLC, the prognostic significance of the tumor microenvironment (TME) immune composition has been revealed using single- or dual-marker staining on sequential tissue sections. Although these studies reveal that relative abundance and localization of immune cells are important parameters, deeper analyses of the NSCLC TME are necessary to refine the potential application of these findings to clinical care. Currently, the complex spatial relationships between cells of the NSCLC TME and potential drivers contributing to its immunologic composition remain unknown.MethodsWe used multispectral quantitative imaging on the lung adenocarcinoma TME in 153 patients with resected tumors. On a single slide per patient, we evaluated the TME with markers for CD3, CD8, CD14, CD19, major histocompatibility complex II (MHCII), cytokeratin, and 4′,6-diamidino-2-phenylindole (DAPI). Image analysis, including tissue segmentation, phenotyping, and spatial localization, was performed.ResultsSpecimens wherein greater than or equal to 5% of lung cancer cells expressed MHCII (MHCIIhi TME) had increased levels of CD4+ and CD8+ T cells and CD14+ cell infiltration. In the MHCIIhi TME, the immune infiltrate was closer to cancer cells and expressed an activated phenotype. Morphologic image analysis revealed cancer cells in the MHCIIhi TME more frequently interfaced with CD4+ and CD8+ T cells. Patients with an MHCIIhi TME experienced improved overall survival (p = 0.046).ConclusionsLung cancer cell-specific expression of MHCII associates with levels of immune cell infiltration, spatial localization, and activation status within the TME. This suggests that cancer cell-specific expression of MHCII may represent a biomarker for the immune system’s recognition and activation against the tumor. 相似文献
13.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
14.
《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
15.
This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway. 相似文献
16.
2019年12月始,新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19)以湖北武汉为中心向全国各地蔓延。目前数据显示,COVID-19合并糖尿病、高血压、肿瘤等基础病的患者病情较为严峻,病死率相对较高。该类患者的临床治疗策略有待进一步深入研究。在此次疫情防治过程中,中西医结合治疗手段于COVID-19的防治及患者基础疾病的兼顾治疗方面展现出了一定的特色及优势。本文结合中医“未病先防,既病防变,瘥后防复”思想,拟从COVID-19合并糖尿病、高血压、肿瘤三个方面,探讨COVID-19爆发形势下合并基础病患者的中医药防治策略。 相似文献
17.
Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment. 相似文献
18.
随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献
19.
The main of this study was to evaluate the mutagenic and carcinogenic potential of (+) – usnic acid (UA), using Somatic Mutation and Recombination Test (SMART) and the test for detecting epithelial tumor clones (wts) in Drosophila melanogaster. Larvae from 72 ± 4 h from Drosophila were fed with UA (5.0, 10.0 or 20.0 mM); urethane (10.0 mM) (positive control); and solvent (Milli-Q water, 1% Tween-80 and 3% ethanol) (negative control). ST cross produced increase in total mutant spots in the individuals treated with 5.0, 10.0 or 20.0 mM of UA. HB cross produced spot frequencies in the concentration of 5.0 mM that were higher than the frequency for the same concentration in the ST cross. In the highest concentrations the result was negative, which means that the difference observed can be attributed, in part, to the high levels of P450, suggesting that increasing the metabolic capacity maximized the toxic effect of these doses. In the evaluation of carcinogenesis using the wts test, the results obtained for the same concentrations of UA show a positive result for the presence of tumors when compared to the negative control. We conclude that UA has recombinogenic, mutagenic and carcinogenic effects on somatic cells in D. melanogaster. 相似文献
20.
James R. Barrett MD Victoria Rendell MD Courtney Pokrzywa MD Alexandra G. Lopez-Aguiar MD John Cannon BA George A. Poultsides MD MS Flavio Rocha MD Angelena Crown MD Eliza Beal MD Timothy Michael Pawlik MD MPH PhD Ryan Fields MD Roheena Z. Panni MD MPHS Paula Smith MD Kamran Idrees MD Clifford Cho MD Megan Beems MD Shishir Maithel MD Sharon Weber MD Daniel Erik Abbott MD 《Journal of surgical oncology》2020,121(7):1067-1073