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   3080篇
  免费   312篇
  国内免费   159篇
耳鼻咽喉   25篇
儿科学   14篇
妇产科学   22篇
基础医学   600篇
口腔科学   638篇
临床医学   155篇
内科学   284篇
皮肤病学   206篇
神经病学   61篇
特种医学   56篇
外国民族医学   1篇
外科学   196篇
综合类   495篇
预防医学   63篇
眼科学   122篇
药学   295篇
中国医学   89篇
肿瘤学   229篇
  2023年   51篇
  2022年   58篇
  2021年   95篇
  2020年   92篇
  2019年   81篇
  2018年   77篇
  2017年   105篇
  2016年   99篇
  2015年   127篇
  2014年   203篇
  2013年   212篇
  2012年   189篇
  2011年   203篇
  2010年   170篇
  2009年   130篇
  2008年   150篇
  2007年   135篇
  2006年   134篇
  2005年   111篇
  2004年   126篇
  2003年   126篇
  2002年   105篇
  2001年   71篇
  2000年   65篇
  1999年   63篇
  1998年   43篇
  1997年   42篇
  1996年   41篇
  1995年   45篇
  1994年   32篇
  1993年   35篇
  1992年   30篇
  1991年   19篇
  1990年   19篇
  1989年   24篇
  1988年   19篇
  1987年   23篇
  1986年   16篇
  1985年   23篇
  1984年   33篇
  1983年   11篇
  1982年   24篇
  1981年   20篇
  1980年   25篇
  1979年   13篇
  1978年   16篇
  1977年   6篇
  1976年   6篇
  1973年   2篇
  1972年   2篇
排序方式: 共有3551条查询结果,搜索用时 15 毫秒
1.
目的研究喉癌肿瘤相关成纤维细胞(CAFs)外泌体表达下调的miRNA-656-3p对喉癌细胞生长和侵袭能力的影响以及丹参酮ⅡA对其调控作用。方法将CAFs外泌体miRNA-656-3p表达上调,制备外泌体上清,检测其对喉癌细胞体外增殖、侵袭能力及细胞周期的影响。检测中药提取物丹参酮ⅡA是否具有类似的上调CAFs外泌体miRNA-656-3p表达的作用,其作用后的CAFs外泌体上清是否具有类似的抑制喉癌增殖和侵袭能力的功效。结果过表达miR-656-3p的CAFs外泌体上清能抑制喉癌细胞的体外增殖和侵袭能力,抑制CCND2的表达,并将喉癌细胞阻滞在G0/G1期。而丹参酮ⅡA也可以上调CAFs外泌体中miR-656-3p的表达水平,其作用后的CAFs外泌体能发挥类似的抑制喉癌细胞体外增殖和侵袭的功效。结论喉癌CAFs外泌体miRNA-656-3p的表达下调促进喉癌细胞的生长和侵袭能力,丹参酮ⅡA可上调CAFs外泌体miR-656-3p的表达,通过后者抑制喉癌细胞的生长和侵袭能力。  相似文献   
2.
《Cancer cell》2022,40(11):1392-1406.e7
  1. Download : Download high-res image (241KB)
  2. Download : Download full-size image
  相似文献   
3.
《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.  相似文献   
4.
5.
6.
《Saudi Dental Journal》2021,33(7):679-686
BackgroundBiocompatibility is an essential property for any dental root repair material that may interact with the surrounding periodontal tissues. We hypothesise that the three mineral trioxide aggregate (MTA) restorative brands ProRoot MTA, MTA Flow and Harvard MTA have similar biocompatibility. To test this hypothesis, we compared the cytotoxic effects of these materials on human gingival fibroblast (GF).MethodsMTA cements were prepared, and after completion of setting, they were incubated in Dulbecco's Modified Eagle Medium for 1 day or 4 days to obtain low and high concentrations of MTA elutes respectively. The elutes of MTA supplemented with fetal bovine serum were added to GF and incubated for 3 days at 37 °C and 5% CO2. Untreated cells were used as control. The cell viability was assessed using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay at 24, 48 and 72 h.ResultsAfter 24 h, the MTT assay showed that both 1- and 4-day elutes of MTA flow and Harvard MTA reduced cell viability significantly compared to control (P < 0.05). After 48 h, the 1-day elute of ProRoot MTA induced GF proliferation (P = 0.0136) while MTA flow and Harvard MTA were similar to control. After 72 h, the 1-day elute of ProRoot MTA and Harvard MTA induced GF proliferation, while the elute of MTA flow was comparable to control. The 4-day elute of Harvard MTA continued to be cytotoxic to GF after 24 h, 48 h, and 72 h incubation, while the 4-day elute of ProRoot MTA and MTA flow were similar to control.ConclusionProRoot MTA and MTA Flow showed comparable biocompatibility. However, the 4-day elute of Harvard MTA was cytotoxic to GF. Further studied are required to assess the cell viability after direct contact with these materials versus eluent in vitro and compare these sealers in the clinical setting.  相似文献   
7.
目的探讨癌相关成纤维细胞(CAFs)在体外的分泌功能及对喉癌细胞Hep-2生物学行为的影响。方法提取江西省肿瘤医院2016-09-09 1例喉鳞状细胞癌手术患者的癌组织及癌旁组织,进行喉癌CAFs及正常成纤维细胞(NFs)的原代培养。ELISA试剂盒测定CAFs和NFs培养上清液中MMP-2、MMP-9的浓度。制备CAFs及NFs条件培养基分别对Hep-2细胞进行培养,CCK-8法检测细胞的增殖情况。采用Transwell法,Hep-2细胞分别与CAFs及NFs进行共培养,设实验组(CAFs共培养组)、对照组(NFs共培养组)和空白组(DMEM培养组),流式细胞法检测Hep-2细胞凋亡率,Transwell侵袭小室法检测Hep-2细胞的侵袭能力。采用SPSS 15.0对数据进行统计学分析。结果 MMP-2于CAFs培养上清液中的浓度为(3.40±0.22)ng/mL,于NFs培养上清液中的浓度为(2.52±0.19)ng/mL,差异有统计学意义,t=-5.246,P=0.006。MMP-9于CAFs培养上清液中的浓度为(164.88±6.54)pg/mL,于NFs培养上清液中的浓度为(114.16±4.48)pg/mL,差异有统计学意义,t=-11.087,P<0.001。CCK-8检测各培养基组的A450值,各培养基组间A450值差异有统计学意义,F培养基=13.977,P培养基<0.001,显示与NFs条件培养基组相比,CAFs条件培养基可促进Hep-2细胞的增殖。流式细胞法检测实验组Hep-2细胞凋亡率为(7.17±1.24)%,而对照组和空白组Hep-2细胞凋亡率则分别为(2.45±0.73)%、(2.05±0.74)%,差异有统计学意义,F=27.664,P=0.001。Transwell法共培养后,检测各组Hep-2穿膜细胞数,实验组为(347.80±23.73)个,对照组和空白组分别为(254.00±46.11)、(191.40±23.67)个,差异有统计学差异,F=28.599,P<0.001。结论 CAFs对Hep-2细胞具有促进增殖、增强侵袭能力以及诱导凋亡的作用,且CAFs中MMP2、MMP-9分泌性表达的增加可能有助于增强Hep-2细胞的侵袭能力。  相似文献   
8.
目的探究肿瘤相关成纤维细胞外泌体对肺癌细胞生长和转移的影响及机制。方法取肺癌患者的癌组织和癌旁组织分离肿瘤相关成纤维细胞(Cancer-associated fibroblasts,CAFs)和成纤维细胞(Normal Fibroblasts,NFs),免疫荧光和Western blot鉴定CAFs和NFs中α-SMA、FSP-1、FAP、Vimentin表达,差速离心法提取CAFs和NFs细胞外泌体,利用透射电镜和Western blot鉴定外泌体,将外泌体与肺癌细胞A549共孵育后检测细胞增殖、迁移、侵袭、细胞凋亡水平,Western blot检测PI3K/AKT/mTOR信号通路激活水平。结果α-SMA、FSP-1、FAP、Vimentin高表达于CAFs;透射电镜和Western blot鉴定外泌体符合其特征;与PBS组相比,与CAFs外泌体共孵育组A549细胞增殖、迁移、侵袭能力显著增加(P<0.001),细胞凋亡水平显著降低(P<0.001),PI3K、AKT、mTOR磷酸化水平显著增加,而与NFs外泌体共孵育后细胞增殖、迁移、侵袭以及凋亡水平无显著变化,PI3K、AKT、mTOR磷酸化水平无显著变化。结论肿瘤相关成纤维细胞外泌体能够通过激活PI3K/AKT/mTOR信号通路,而促进肺癌细胞的生长和转移。  相似文献   
9.
BACKGROUNDDiffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients.AIMTo screen the novel mediators involved in the development of DLBCL.METHODSThe GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal.RESULTSThe top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin (A2M), cathepsin B (CTSB), FN1, matrix metallopeptidase 9 (MMP9), and SPARC. The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of A2M, FN1, CTSB, MMP9, and SPARC were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positive correlation with the development of DLBCL. More interestingly, the five genes had a significant correlation with the stromal infiltration scores. The correlation analysis between the fives genes and CAFs also showed a significant value, among which the top two genes, FN1 and SPARC, had a remarkable co-expression pattern.CONCLUSIONThe top DEGs were identified, and the five hub genes were overexpressed in DLBCL. Furthermore, the gene alterations were confirmed and the positive correlation with tumor purity revealed the overexpression of the five genes and close association with the development of DLBCL. More interestingly, the five genes were positively correlated with stromal infiltration, especially in CAFs. The top two genes, FN1 and SPARC, showed a co-expression pattern, which indicates their potential as novel therapeutic targets for DLBCL.  相似文献   
10.
《Vaccine》2021,39(14):1933-1942
The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.  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