全文获取类型
收费全文 | 2523篇 |
免费 | 293篇 |
国内免费 | 127篇 |
专业分类
化学 | 2427篇 |
力学 | 6篇 |
综合类 | 18篇 |
数学 | 90篇 |
物理学 | 402篇 |
出版年
2024年 | 7篇 |
2023年 | 67篇 |
2022年 | 506篇 |
2021年 | 420篇 |
2020年 | 236篇 |
2019年 | 109篇 |
2018年 | 75篇 |
2017年 | 103篇 |
2016年 | 153篇 |
2015年 | 154篇 |
2014年 | 135篇 |
2013年 | 190篇 |
2012年 | 135篇 |
2011年 | 93篇 |
2010年 | 66篇 |
2009年 | 90篇 |
2008年 | 61篇 |
2007年 | 62篇 |
2006年 | 46篇 |
2005年 | 33篇 |
2004年 | 24篇 |
2003年 | 31篇 |
2002年 | 20篇 |
2001年 | 15篇 |
2000年 | 19篇 |
1999年 | 20篇 |
1998年 | 12篇 |
1997年 | 16篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1981年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有2943条查询结果,搜索用时 15 毫秒
1.
西咪替丁的应用进展 总被引:2,自引:0,他引:2
劳英 《宁波大学学报(理工版)》2002,15(2):89-92
综述了近年来国内外报道的H2受体抗拮剂-西咪替丁应用于除治疗消化性溃疡以外的其他疾病的进展情况,以其为临床用药提供参考。 相似文献
2.
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
3.
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
4.
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
5.
Yangke Wanyan Xixi Xu Kehang Liu Huidan Zhang Junai Zhen Rong Zhang Jumei Wen Ping Liu Yuqing Chen 《Molecules (Basel, Switzerland)》2020,25(23)
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
6.
Kringen P Egedal S Pedersen JC Harbitz TB Tveit KM Berg K Børresen-Dale AL Andersen TI 《Electrophoresis》2002,23(24):4085-4091
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
7.
ZHU Zhi-cheng SUN Mei ZHANG Xing-yi LIU Ke-xiang SHI Dong-lei LI Jin-dong SU Ji-quan XU Yue-chi FU Xue-qi 《高等学校化学研究》2007,23(3):289-296
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
8.
Photokilling Squamous Carcinoma Cells SCCVII with Ultrafine Particles of Selected Metal Oxides 总被引:1,自引:0,他引:1
Ivanković Siniša Gotić Marijan Jurin Mislav Musić Svetozar 《Journal of Sol-Gel Science and Technology》2003,27(2):225-233
The ability of ultrafine particles of TiO2, WO3 and iron-doped TiO2 to kill cancer cells in the presence of UV irradiation was investigated. The best photokilling effect on carcinoma cells SCVII cultured in vitro showed iron-doped TiO2 ultrafine particles synthesized by the sol-gel procedure with starting chemicals Ti(IV)-isopropoxide and anhydrous Fe(II)-acetate. It was found that a small particle size and high dispersity influenced citotoxicity and photocatalytic efficiency. The remarkable photokiling effect of highly iron-doped TiO2 ultrafine particles (the molar ratio Fe/Ti = 0.136) in the presence of UV irradiation was observed. The influence of ultrafine metal oxide particles on the inhibition of cancer cell proliferation was measured using a 3H-thymidine incorporation test. The possible mechanism involved in the photokilling of carcinoma cells with ultrafine particles of selected metal oxides was discussed. 相似文献
9.
10.
Erem Bilensoy Yasemin Çırpanlı Murat Şen A. Lale Doğan Sema Çalış 《Journal of inclusion phenomena and macrocyclic chemistry》2007,57(1-4):363-370
Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic® F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of β-CD and HP-β-CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose. 相似文献