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   3058篇
  免费   358篇
  国内免费   177篇
化学   2209篇
力学   6篇
综合类   18篇
数学   88篇
物理学   375篇
综合类   897篇
  2024年   8篇
  2023年   57篇
  2022年   361篇
  2021年   432篇
  2020年   245篇
  2019年   124篇
  2018年   93篇
  2017年   119篇
  2016年   173篇
  2015年   181篇
  2014年   182篇
  2013年   217篇
  2012年   175篇
  2011年   130篇
  2010年   104篇
  2009年   120篇
  2008年   106篇
  2007年   101篇
  2006年   82篇
  2005年   73篇
  2004年   61篇
  2003年   63篇
  2002年   55篇
  2001年   46篇
  2000年   46篇
  1999年   36篇
  1998年   42篇
  1997年   31篇
  1996年   23篇
  1995年   25篇
  1994年   19篇
  1993年   10篇
  1992年   13篇
  1991年   8篇
  1990年   4篇
  1989年   11篇
  1988年   3篇
  1987年   4篇
  1986年   3篇
  1985年   1篇
  1984年   3篇
  1981年   1篇
  1976年   1篇
  1955年   1篇
排序方式: 共有3593条查询结果,搜索用时 15 毫秒
11.
描述了Laminin五肽(YIGSR)对胃癌细胞系MGc-803的体外抑制作用,在多肽浓度为1mg/ml时抑制率高达73%.抑制作用的机理可能是Laminin五肽竞争了肿瘤细胞上Laminin受体,从而封闭了肿瘤细胞对基底膜的结合及增殖.因此,利用Laminin五肽一类的药物有可能为肿瘤术后防止扩散提供一个新方法.  相似文献   
12.
分析了1994 ̄1995年在浙江医科大学附属第一医院门诊的口腔鳞癌患者的血清的硒浓度,结果表明口腔鳞癌患者血清硒浓度极显著低于正常人群,而手术后患者血清硒浓度又极显著高于手术前患者。  相似文献   
13.
Introduction TheTSP50genehasbeenidentifiedasoneofthe testis specificoncogenes,whichisexpressedathigh levelsinapproximately92%ofhumanbreastcancer samples,makingitanattractivemolecularmarkerand apotentialtargetfordiagnosisandtherapy[1].Itisho mologoustomany…  相似文献   
14.
1 INTRODUCTION Hexamethylenebis[acetamide] (HMBA) is an effective agent in phaseⅡclinical trial[1] that induces differentiation of certain types of tumors to nonmalignant phenotypes. In an attempt to discover more efficient inducers, a number of derivatives of HMBA have been synthesized and evaluated in vitro[2, 3]. The results proved that increasing the number of functional groups could enhance the anticancer activity. In addition, it was evident that compounds with six methylene i…  相似文献   
15.
In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors.  相似文献   
16.
Inhibition of the glycolytic pathway is a critical strategy in anticancer therapy because of the role of aerobic glycolysis in cancer cells. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) has shown potential in combination with other anticancer agents. Buforin IIb is an effective antimicrobial peptide (AMP) with broad-spectrum anticancer activity and selectivity. The efficacy of combination treatment with 2-DG and buforin IIb in prostate cancer remains unknown. Here, we tested the efficacy of buforin IIb as a mitochondria-targeting AMP in the androgen-independent human prostate cancer cell line DU145. Combining 2-DG with buforin IIb had a synergistic toxic effect on DU145 cells and mouse xenograft tumors. Combination treatment with 2-DG and buforin IIb caused stronger proliferation inhibition, greater G1 cell cycle arrest, and higher apoptosis than either treatment alone. Combination treatment dramatically decreased L-lactate production and intracellular ATP levels, indicating severe inhibition of glycolysis and ATP production. Flow cytometry and confocal laser scanning microscopy results indicate that 2-DG may increase buforin IIb uptake by DU145 cells, thereby increasing the mitochondria-targeting capacity of buforin IIb. This may partly explain the effect of combination treatment on enhancing buforin IIb-induced apoptosis. Consistently, 2-DG increased mitochondrial dysfunction and upregulated Bax/Bcl-2, promoting cytochrome c release to initiate procaspase 3 cleavage induced by buforin IIb. These results suggest that 2-DG sensitizes prostate cancer DU145 cells to buforin IIb. Moreover, combination treatment caused minimal hemolysis and cytotoxicity to normal WPMY-1 cells. Collectively, the current study demonstrates that dual targeting of glycolysis and mitochondria by 2-DG and buforin IIb may be an effective anticancer strategy for the treatment of some advanced prostate cancer.  相似文献   
17.
A promising liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) for analysis of the sulfates of 5alpha-androgen, androsterone and epiandrosterone (A-S and EpiA-S) in human serum was developed. The method was used to assess one of the markers of 5alpha-reductase activity of males including patients with prostate cancer (PC). After deproteinization with acetonitrile, the androgen sulfates and the internal standard, [7,7,16,16-2H4]dehydroepiandrosterone-S, were extracted from human serum using a solid-phase extraction cartridge and washed with hexane. The extract was reconstituted and applied to the LC/ESI-MS system operated in the selected ion monitoring mode. The method was validated over the range 0.02-5 microg/mL (A-S) and 0.005-1.5 microg/mL (EpiA-S) using 10 microL of human serum. The method was a concise procedure without chemical or enzymatic hydrolysis of the conjugates, purification by high-performance liquid chromatography and/or derivatization, and proved to be satisfactory in its reproducibility and accuracy. The levels of these androgen sulfates tended to decrease during aging, and the A-S levels in the sera obtained from both healthy males and patients with PC were correlated with their EpiA-S levels.  相似文献   
18.
Efficient mutation scanning techniques are needed for the rapid detection of novel disease-associated mutations and rare-sequence variants of putative importance. The large size of the breast cancer 1 gene (BRCA1) and the many mutations found throughout its entire coding sequence make screening for mutations in this gene particularly challenging. We have developed a method for screening exon 11 of the BRCA1 gene based on restriction enzyme digestion of fluorescence-labeled polymerase chain reaction (PCR) products followed by single-strand conformation polymorphism (SSCP) using an automated capillary electrophoresis system, denoted capillary restriction endonuclease fingerprinting (REF)-SSCP electrophoresis. Using this strategy on a control set of samples, we were able to detect 17 of 18 known sequence alterations. The method was then applied to screen 73 Norwegian females with family histories of breast and/or ovarian cancer. A total of 172 sequence alterations were detected, including substitutions, insertions, and deletions. One novel substitution of unknown function was identified. Sequencing of all samples negative in the capillary REF-SSCP system gave no additional mutations confirming the high sensitivity of the described methodology. Capillary REF-SSCP electrophoresis appeared as a technically convenient technique, requiring amplification of fewer PCR fragments than traditional SSCP. The novel strategy allows high-throughput mutation scanning without radioactive labeling and polyacrylamide gel electrophoresis (PAGE).  相似文献   
19.
This study objective was to express and characterize the catalytic domain of the human T cell protein tyrosine phosphatase(△TC-PTP) and to study immunohistochemically the expression of △TC-PTP in human non-small cell lung cancers. △TC-PTP gene was PCR amplified with the cDNA of human TC-PTP as template, and cloned into the pT7 expression vector. The recombinant pT7-△TC-PTP was expressed in E. coli Rosetta ( DE3 ) host cells and puri- fied. The enzymatic characteristics of △TC-PTP including enzyme activity and kinetics assay were measured. The antiserum was prepared by immunizing rabbit with the purified recombinant △TC-PTP. Rabbit polyclonal antibody against △TC-PTP was purified by PVDF immobilized antigen affinity chromatography. Immunohistochemical staining of lung cancer tissues was performed with antibody against △TC-PTP protein. △TC-PTP gene was correctly cloned, expressed, and purified. The recombinant △TC-PTP had a highly catalytic activity of PTPase. Squamous cell lung carcinoma showed a significantly higher expression rate of △TC-PTP (76. 92%, 10/13 ) than adenocarcinoma (57.14%, 4/7) and normal lung tissue(20%, 1/5 ). This study represents the first demonstration that △TC-PTP is highly expressed in human squamous cell lung carcinomas. In addition, this study provides an important basis for further studying the biological function of TC-PTP and its relationship with lung carcinomas and other diseases.  相似文献   
20.
鼻咽癌患者治疗过程中头发微量元素的变化   总被引:1,自引:0,他引:1  
对比了30名健康人与100名初诊、三个月后复诊及六个月后复诊的鼻咽癌患者头发中的11种微量元素的含量。发现病人的锌(Zn)、铜(Cu)、锰(Mn)及钴(Co)的含量都比健康人低,而病人的钛(Ti)及砷(As)含量则偏高。但经过三至六个月电疗及化疗之后,这些元素的含量普遍与健康人差异变小,这似乎是成功治疗的一个反映。  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