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   5854篇
  免费   584篇
  国内免费   237篇
耳鼻咽喉   37篇
儿科学   116篇
妇产科学   97篇
基础医学   1053篇
口腔科学   128篇
临床医学   396篇
内科学   1102篇
皮肤病学   132篇
神经病学   593篇
特种医学   103篇
外科学   602篇
综合类   713篇
预防医学   161篇
眼科学   108篇
药学   750篇
  1篇
中国医学   152篇
肿瘤学   431篇
  2023年   74篇
  2022年   79篇
  2021年   117篇
  2020年   170篇
  2019年   235篇
  2018年   193篇
  2017年   222篇
  2016年   257篇
  2015年   270篇
  2014年   430篇
  2013年   475篇
  2012年   398篇
  2011年   394篇
  2010年   333篇
  2009年   309篇
  2008年   307篇
  2007年   316篇
  2006年   276篇
  2005年   231篇
  2004年   180篇
  2003年   198篇
  2002年   181篇
  2001年   128篇
  2000年   125篇
  1999年   98篇
  1998年   63篇
  1997年   76篇
  1996年   59篇
  1995年   68篇
  1994年   52篇
  1993年   41篇
  1992年   42篇
  1991年   56篇
  1990年   30篇
  1989年   20篇
  1988年   21篇
  1987年   21篇
  1986年   11篇
  1985年   25篇
  1984年   15篇
  1983年   11篇
  1982年   13篇
  1981年   9篇
  1980年   11篇
  1979年   9篇
  1978年   4篇
  1977年   7篇
  1976年   7篇
  1974年   3篇
  1973年   2篇
排序方式: 共有6675条查询结果,搜索用时 17 毫秒
1.
Introduction: Lichen planus (LP) is a relatively common chronic mucocutaneous disease that affects the skin and mucous membranes, including oral mucosa. The etiology of the disease is unknown. Some evidence suggests that the immune system and inflammation may play a role in the formation and progression of lichen planus. Some authorities believe that LP is a precancerous condition. The purpose of this study was to investigate the serum levels of the inflammatory cytokines CRP, IL-1, IL-6, and TNF- in patients with oral lichen planus and oral squamous cell carcinoma (OSCC), as well as to assess the relationship between these cytokine levels and clinical symptoms. Methods: A total of 75 subjects, with 25 in each group of oral lichen planus, healthy control, and oral squamous cell carcinoma, participated in this cross-sectional study. Serum levels of IL-1α, TNF-α, IL-6, and CRP were determined and compared. In comparison to the healthy control group, the lichen planus and oral squamous cell carcinoma groups had higher levels of CRP, IL-1α, IL-6, and TNF-α. Results: We discovered that the mean mRNA and protein levels of CRP, IL-1α, IL-6, and TNF-α were significantly higher in the blood and tissue of lichen planus and OSCC patients than in normal controls. Conclusion: Higher levels of CRP, IL-1α, IL-6, and TNF-α may be linked to OLP and oral carcinogenesis. More research with larger groups is required.  相似文献   
2.
Adiponectin is the major adipocytes-secreted protein involved in obesity-related breast cancer growth and progression. We proved that adiponectin promotes proliferation in ERα-positive breast cancer cells, through ERα transactivation and the recruitment of LKB1 as ERα-coactivator. Here, we showed that adiponectin-mediated ERα transactivation enhances E-cadherin expression. Thus, we investigated the molecular mechanism through which ERα/LKB1 complex may modulate the expression of E-cadherin, influencing tumor growth, progression and distant metastasis. We demonstrated that adiponectin increases E-cadherin expression in ERα-positive 2D and higher extent in 3D cultures. This occurs through a direct activation of E-cadherin gene promoter by ERα/LKB1-complex. The impact of E-cadherin on ERα-positive breast cancer cell proliferation comes from the evidence that in the presence of E-cadherin siRNA the proliferative effects of adiponectin is no longer noticeable. Since E-cadherin connects cell polarity and growth, we investigated if the adiponectin-enhanced E-cadherin expression could influence the localization of proteins cooperating in cell polarity, such as LKB1 and Cdc42. Surprisingly, immunofluorescence showed that, in adiponectin-treated MCF-7 cells, LKB1 and Cdc42 mostly colocalize in the nucleus, impairing their cytosolic cooperation in maintaining cell polarity. The orthotopic implantation of MCF-7 cells revealed an enhanced E-cadherin-mediated breast cancer growth induced by adiponectin. Moreover, tail vein injection of MCF-7 cells showed a higher metastatic burden in the lungs of mice receiving adiponectin-treated cells compared to control. From these findings it emerges that adiponectin treatment enhances E-cadherin expression, alters cell polarity and stimulates ERα-positive breast cancer cell growth in vitro and in vivo, sustaining higher distant metastatic burden.  相似文献   
3.
目的: 借助多种癌症生物信息数据库研究乳腺癌组织中缺氧诱导因子1亚基α (HIF1A)的表达水平及其与乳腺癌患者预后及肿瘤免疫细胞浸润的关系。 方法: 利用Oncomine、人类蛋白质图谱、基因表达谱交互式分析(GEPIA)及TCGA数据库分析HIF1A基因在乳腺癌组织中的表达及其与患者预后、临床病理特征的关系,并在中国人乳腺癌组织标本(选用2011年1月至2015年12月中国武汉大学人民医院手术切除的93例乳腺癌组织和14例良性乳腺疾病组织)中进行验证。对HIF1A高低表达组间的差异基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,用Cibersort R软件评估HIF1A高低表达样本中免疫细胞浸润丰度差异。 结果: 生物信息数据显示,HIF1A在乳腺癌组织中高表达,预示着患者DFS预后更好(P<0.05)。HIF1A的表达与雌激素受体(ERP)、孕激素受体(PR)和人表皮生长因子受体2 (HER2)表达相关(均P<0.05)。GO生物功能及KEGG通路富集分析结果提示,HIF1A可能参与肿瘤免疫调节等生物活动。使用Cibersort分析结果显示,HIF1A与肿瘤免疫细胞浸润之间具有相关性(均P<0.01),发现活化记忆CD4 + T细胞、M0和M1型巨噬细胞与HIF1A表达呈正相关,在乳腺癌组织中高表达,Treg细胞、活化NK细胞、M2型巨噬细胞与HIF1A表达呈负相关(均P<0.01)。 结论: HIF1A参与调节肿瘤微环境的免疫活性,与乳腺癌患者DFS相关,其可能成为乳腺癌分级诊断、免疫治疗和预后判断的生物标志物。  相似文献   
4.
5.
6.
Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.  相似文献   
7.
《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.  相似文献   
8.
背景与目的:不育α基序结构域和组氨酸/天冬氨酸残基双联体结构域包涵蛋白1(sterile alpha motif and histidine/aspartic acid domain-containing protein 1,SAMHD1)具有抑制多种肿瘤细胞生长的作用,但其调节肝细胞癌(hepatocellular carcinoma,HCC)细胞增殖的作用及机制尚未见报道。探究SAMHD1调控p27的表达对HCC细胞Huh7的增殖、凋亡和细胞周期的影响。方法:首先通过蛋白质印迹法(Western blot)检测正常肝细胞和不同类型HCC细胞中SAMHD1的表达情况。利用基因修饰技术构建过表达SAMHD1、dNTP酶活性位点突变体(SAMHD1-D207N)和磷酸化位点突变体(SAMHD1-T592E)的重组质粒,然后利用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测过表达SAMHD1及其突变体或siRNA干扰沉默SAMHD1对HCC细胞增殖的影响,采用流式细胞术检测细胞周期与细胞凋亡情况。在癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中分析SAMHD1和p27表达的相关性。结果:HCC细胞中SAMHD1表达上调,过表达SAMHD1、SAMHD1-D207N和SAMHD1-T592E可以抑制Huh7细胞增殖,细胞周期停滞在G 1 /G 0 期;相反,干扰SAMHD1后细胞增殖加快,细胞周期停滞在G 2 /M期。机制研究表明,SAMHD1上调细胞周期蛋白激酶抑制因子p27的表达。在HCC组织中,p27的表达与SAMHD1表达呈正相关。结论:过表达SAMHD1可以上调p27的表达,导致细胞周期停滞在G 1 /G 0 期,从而抑制HCC细胞增殖,这种抑制作用不依赖于其dNTP酶活性和磷酸化修饰。  相似文献   
9.
目的:研究胰岛素样生长因子-2(insulin like growth factor,IGF-2)、甲胎蛋白(alpha fetoprotein,AFP)、碱性磷酸酶(alkaline phosphatase,ALP)、r-谷氨酰转肽酶(r-glutamyl transferase,r-GT)在原发性肝癌模型小鼠血清中的表达水平。方法:选择SD健康雄性小鼠35只,按照随机数字法分为正常组和原发性肝癌组两组,分别有10只和25只小鼠。正常组小鼠不做任何处理,原发性肝癌组小鼠制成原发性肝癌模型,造模成功的共22只小鼠。免疫透射比浊法检测IGF-2、电化学发光免疫分析检测AFP的血清水平、双抗体夹心法检测ALP、r-GT水平表达、荧光定量RT-PCR技术检测IGF-2 mRNA、AFP mRNA、ALP mRNA、r-GT mRNA表达水平。结果:正常组小鼠肝组织细胞大小均匀,形态一致;原发性肝癌组小鼠肝组织细胞大小不等,细胞核形态多样,多有核分裂现象。原发性肝癌组小鼠的血清中IGF-2和IGF-2 mRNA水平均显著高于正常组的健康小鼠(P<0.05);原发性肝癌组小鼠的血清中AFP和AFP mRNA水平均显著高于正常组的健康小鼠(P<0.05);原发性肝癌组小鼠的血清中ALP和ALP mRNA水平均显著高于正常组的健康小鼠(P<0.05);原发性肝癌组小鼠的血清中r-GT和r-GT mRNA水平均显著高于正常组的健康小鼠(P<0.05)。结论:原发性肝癌模型小鼠血清中IGF-2、AFP、ALP、r-GT水平都呈高水平表达,检测其血清中的水平对原发性肝癌的诊断有重要价值。  相似文献   
10.
分析不同手术入路途径对胸中段老年食管癌患者的综合疗效,将160例患者按照不同治疗方法分为左胸路径组70例和右胸路径组90例。左胸路径组患者行左胸两切口入路手术,右胸路径组患者行右胸三切口手术入路。结果显示:与左胸路径组相比,右胸路径组的手术时间、术中出血量及VAS评分明显升高(P<0.05),淋巴结清扫率明显升高(P<0.05),1年转移率、3年转移率明显降低而1年生存率和3年生存率明显升高(P<0.05),而术后引流时间及住院时间无明显差异性;两组患者治疗后血清中VEGF、VEGFR、HIFα水平均明显降低而PTEN水平明显升高(P<0.05),且右胸路径组患者的上述指标变化更显著(P<0.05)。因此,不同手术入路途径对胸中段老年食管癌患者的临床效果及血清中VEGF-HIFα-PTEN表达水平和肿瘤转移有不同影响,临床上应合理选择。  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