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   628篇
  免费   53篇
  国内免费   22篇
化学   244篇
力学   14篇
综合类   6篇
数学   15篇
物理学   77篇
综合类   347篇
  2025年   6篇
  2024年   13篇
  2023年   15篇
  2022年   73篇
  2021年   53篇
  2020年   31篇
  2019年   14篇
  2018年   15篇
  2017年   20篇
  2016年   20篇
  2015年   19篇
  2014年   29篇
  2013年   30篇
  2012年   29篇
  2011年   39篇
  2010年   14篇
  2009年   32篇
  2008年   26篇
  2007年   21篇
  2006年   19篇
  2005年   18篇
  2004年   23篇
  2003年   20篇
  2002年   13篇
  2001年   18篇
  2000年   19篇
  1999年   11篇
  1998年   12篇
  1997年   9篇
  1996年   5篇
  1995年   6篇
  1994年   7篇
  1993年   3篇
  1992年   5篇
  1991年   3篇
  1990年   4篇
  1989年   5篇
  1988年   1篇
  1985年   2篇
  1980年   1篇
排序方式: 共有703条查询结果,搜索用时 0 毫秒
91.
    
Cancer progression is linked to aberrant protein glycosylation due to the overexpression of several glycosylation enzymes. These enzymes are underexploited as potential anticancer drug targets and the development of rapid-screening methods and identification of glycosylation inhibitors are highly sought. An integrated bioinformatics and mass spectrometry-based glycomics-driven glycoproteomics analysis pipeline was performed to identify an N-glycan inhibitor against lung cancer cells. Combined network pharmacology and in silico screening approaches were used to identify a potential inhibitor, pictilisib, against several glycosylation-related proteins, such as Alpha1-6FucT, GlcNAcT-V, and Alpha2,6-ST-I. A glycomics assay of lung cancer cells treated with pictilisib showed a significant reduction in the fucosylation and sialylation of N-glycans, with an increase in high mannose-type glycans. Proteomics analysis and in vitro assays also showed significant upregulation of the proteins involved in apoptosis and cell adhesion, and the downregulation of proteins involved in cell cycle regulation, mRNA processing, and protein translation. Site-specific glycoproteomics analysis further showed that glycoproteins with reduced fucosylation and sialylation were involved in apoptosis, cell adhesion, DNA damage repair, and chemical response processes. To determine how the alterations in N-glycosylation impact glycoprotein dynamics, modeling of changes in glycan interactions of the ITGA5–ITGB1 (Integrin alpha 5-Integrin beta-1) complex revealed specific glycosites at the interface of these proteins that, when highly fucosylated and sialylated, such as in untreated A549 cells, form greater hydrogen bonding interactions compared to the high mannose-types in pictilisib-treated A549 cells. This study highlights the use of mass spectrometry to identify a potential glycosylation inhibitor and assessment of its impact on cell surface glycoprotein abundance and protein–protein interaction.  相似文献   
92.
    
Lung cancer is the leading cause of cancer-related deaths globally. Despite current treatment approaches that include surgery, chemotherapy, radiation and immunotherapies, lung cancer accounted for 1.79 million deaths worldwide in 2020, emphasizing the urgent need to find novel agents and approaches for more effective treatment. Traditionally, chemicals derived from plants, such as paclitaxel and docetaxel, have been used in cancer treatment, and in recent years, research has focused on finding other plant-derived chemicals that can be used in the fight against lung cancer. Ursolic acid is a polyphenol found in high concentrations in cranberries and other fruits and has been demonstrated to have anti-inflammatory, antioxidant and anticancer properties. In this review, we summarize recent research examining the effects of ursolic acid and its derivatives on lung cancer. Data from in vitro cell culture and in vivo animal studies show potent anticancer effects of ursolic acid and indicate the need for clinical studies.  相似文献   
93.
    
Protein arginine methyltransferase 5 (PRMT5) is a popular anticancer target that regulates histone or nonhistone methylation and is linked to the development and poor prognosis of non-small cell lung cancer. PRMT5 inhibitors have shown great promise in clinical trials as a cancer therapy. However, most inhibitors reported recently act in a SAM-competitive mode and lack structural diversity. In this paper, a novel non-SAM inhibitor, 3039-0164, was discovered by the structure-based virtual screening method. The binding mechanism of 3039-0164 to PRMT5 was revealed via molecular docking and molecular dynamics simulations. 3039-0164 inhibited PRMT5 enzymatic activity, downregulated the expression of PRMT5 downstream target genes (FGFR3 and eIF4E), and blocked the activation of the PI3K/AKT/mTOR and ERK signaling pathways. The discovery of 3039-0164 provides precise and creative hit compounds for the design optimization of PRMT5 lead compounds in non-small cell lung cancer.  相似文献   
94.
    
Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which was manifested by reducing the levels of serum lung injury indicators (C3, hs-CRP, and GGT), reducing the levels of inflammatory factors (TNF-α, IL-1β, and IL-6), and increasing the activities of antioxidant enzymes (SOD and CAT) in the lung. Furthermore, PLE had the typical characteristics of pyran-type linked by β-type glycosidic linkages. The conclusions indicated that PLE could be used as functional foods and natural drugs in preventing ALI.  相似文献   
95.
    
Screening and diagnosis of early-stage lung cancer is low worldwide, and when lung cancer progresses to late stage, it will greatly affect the treatment and survival time of patients. Therefore, the development of an affordable and accurate diagnostic technique is critical for lung cancer patients. In this study, we analyzed and verified the changes of substance composition in the serum of early-stage lung cancer patients and proposed an improved ResNeXt model to achieve accurate classification of serum Raman spectra of lung cancer. The robustness of the model is improved by adding different decibels of Gaussian white noise and spectral offset to augment the data, trying to process the augmented data with various pre-processing methods, and inputting the pre-processed data into the improved ResNeXt model, the improved ResNeXt model still shows the optimal performance after sufficient comparison experiments with three other more advanced deep learning models. The experimental results show that the improved ResNeXt model is very suitable for the classification of early-stage lung cancer serum Raman spectra and may provide a reference for future early screening studies of other cancers.  相似文献   
96.
以牡蛎(Saccostrea cucullata)体内分离提取出的牡蛎天然低分子活性多肽(BPO-L,Bioactive Peptides of Oyster in Peak L)为效应物,观察研究BPO-L对人肺腺癌细胞形态和超微结构的影响.光镜观察显示经0.1mg/mL BPO-L处理后的A549细胞体积增大,趋于扁平铺展状态,细胞核质比例变小,核仁数量减少.透射电镜观察显示经0.1mg/mL BPO-L处理后的A549细胞核形态较规则,细胞核内异染色质减少,常染色质增多;细胞质内线粒体数量增多,结构较为一致,高尔基体呈较为典型发达状态,并出现粗面内质网增多和多聚核糖体减少等变化.结果表明,BPO-L能有效改变人肺腺癌细胞的恶性形态与超微结构特征,对肺癌细胞具有一定的诱导分化作用.  相似文献   
97.
转录靶向性KDR启动子调控双自杀基因治疗肺癌的实验研究   总被引:2,自引:0,他引:2  
从人肺癌细胞株中克隆KDR基因的启动子(kinasedomainreceptorpromotor,KDRp),构建KDR基因启动子调控的双自杀基因(CDglyTK)真核表达质粒pcDNA3-KDRp-CdglyTK,将其导入ECV304、L9981和NL9980细胞,建立相应的转基因细胞系,并应用不同的前药处理。体内、外实验结果显示:KDR启动子调控的双自杀基因在KDR高表达人肺癌细胞和人脐静脉内皮细胞靶向表达,而在KDR不表达的正常细胞或正常血管内皮细胞中未检测到双自杀基因表达;联合应用5-FC和GCV处理,对转双自杀基因细胞的杀伤作用显著高于单独应用5-FC或GCV,且二者显示了良好的药物协同作用。  相似文献   
98.
人正常胎肺细胞用含10%小牛血清的MEM培养液原代培养,后用无血清的199培养液继续培养.硝酸纤维膜的斑点酶联免疫印迹法测定显示所收集的无血清培养液中含有能与人重组血小板生成素单抗结合的蛋白质.免疫细胞化学检测发现培养的肺细胞与血小板生成素单抗有明显阳性反应.用小鼠骨髓乙酰胆碱酯酶阳性细胞法测定肺细胞在不同培养时间所收集的培养液促血小板生成活性的大小,结果显示收集的培养液有明显刺激活性并且其活性与肺细胞的密度有相关性.  相似文献   
99.
在分析了滚球搜索算法对近胸膜肺结点的搜索效果后,根据近胸膜肺结点是由不确定的肺区边缘点及其对应的特征点组成,提出了基于模糊连接度的搜索算法。利用肺区边缘关联结点之间的欧氏距离、肺区边缘关联点之间的路径、标记值和模糊连接度四个参数来描述近胸膜肺结点的属性特征,实现近胸膜肺结点的分割。通过对大量的图片进行测试,实验数据表明,该方法在搜索关联结点方面取得了较好的效果。  相似文献   
100.
设计合成了一系列新型的N1-(5-取代基-1,3,4-噻二唑-2-基)-N3-取代苯基-脲类化合物,并测定了它们的抗肿瘤活性.标题化合物对肿瘤转移的生物活性实验是以荷Lewis肺癌小鼠为模型的.生物活性表明部分标题化合物对肿瘤的转移和肿瘤生长具有较好的抑制作用.其结构经元素分析、红外光谱及1H NMR确证.  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