全文获取类型
收费全文 | 340篇 |
免费 | 24篇 |
国内免费 | 9篇 |
专业分类
化学 | 269篇 |
力学 | 2篇 |
综合类 | 3篇 |
数学 | 14篇 |
物理学 | 85篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 92篇 |
2020年 | 39篇 |
2019年 | 14篇 |
2018年 | 12篇 |
2017年 | 15篇 |
2016年 | 12篇 |
2015年 | 11篇 |
2014年 | 11篇 |
2013年 | 27篇 |
2012年 | 14篇 |
2011年 | 12篇 |
2010年 | 9篇 |
2009年 | 22篇 |
2008年 | 8篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有373条查询结果,搜索用时 15 毫秒
101.
Saeb Aliwaini Bassam Abu Thaher Ihab Al-Masri Nabil Shurrab Said El-Kurdi Dieter Schollmeyer Basem Qeshta Mariam Ghunaim Ren Csuk Stefan Laufer Lars Kaiser Hans-Peter Deigner 《Molecules (Basel, Switzerland)》2021,26(13)
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR. 相似文献
102.
Curcumin is an anti‐cancerous agent, but its low‐solubility limits its clinical use. The relationship between deregulation of miRNAs and their targets suggested that miRNAs can be interest targets of curcumin in treatment of different cancers. In this study, to overcome essential defects of the clinical usage of this golden drug, curcumin‐encapsulated polymersome nanoparticles (CPNs) have been developed, and the cytotoxicity effects were studied on MDA‐MB‐231 breast cancer cells. The expression level of miR‐182/125b and the expression pattern of some potential targets in apoptotic pathway, predicted by in silico approaches, were analyzed by RT‐qPCR in CPNs‐treated and untreated cells. Moreover, the amount of CASP9 and CASP8 proteins were determined by Western blotting. The effect of CPNs on cell migration were studied by scratch test and the level of EGFR, E‐cadherin, and beta‐catenin proteins were monitored in CPNs‐treated and untreated cells by western blotting. RT‐qPCR analysis identified the downregulation of miR‐125b and miR‐182 in CPNs‐treated cells and the upregulation of some predicted apoptotic target genes such as P53, CASP9 and BAX after 24 hours. Western blotting confirmed the effects of curcumin on the increase of cleaved CASP9 protein. Based on data from the current experiment, the migration of MDA‐MB‐231 cells was decreased after CPNs treatment. According to the results, CPNs, as suitable and compatible nanocarriers, can deliver curcumin into cancerous cells more effectively and can increase the therapeutic effects of curcumin on MDA‐MB‐231 cells partly by suppression of miR‐125b and miR‐182 as well as induction of apoptosis and inhibition of metastatic progression. 相似文献
103.
Lifu Xiao Chuanqi Wang Chen Dai Laurie E. Littlepage Jun Li Zachary D. Schultz 《Angewandte Chemie (International ed. in English)》2020,59(9):3439-3443
Metabolomics is a powerful systems biology approach that monitors changes in biomolecule concentrations to diagnose and monitor health and disease. However, leading metabolomics technologies, such as NMR and mass spectrometry (MS), access only a small portion of the metabolome. Now an approach is presented that uses the high sensitivity and chemical specificity of surface‐enhanced Raman scattering (SERS) for online detection of metabolites from tumor lysates following liquid chromatography (LC). The results demonstrate that this LC‐SERS approach has metabolite detection capabilities comparable to the state‐of‐art LC‐MS but suggest a selectivity for the detection of a different subset of metabolites. Analysis of replicate LC‐SERS experiments exhibit reproducible metabolite patterns that can be converted into barcodes, which can differentiate different tumor models. Our work demonstrates the potential of LC‐SERS technology for metabolomics‐based diagnosis and treatment of cancer. 相似文献
104.
Fengying Ye Qisheng Zhong Yanshan Liang Ting Zhou 《Journal of separation science》2020,43(9-10):1800-1807
A lyophilization?supercritical fluid extraction coupled with supercritical fluid chromatography?quadrupole tandem mass spectrometry online method was developed for the determination of lipid mediators in breast cancer cells. Supercritical fluid extraction was applied to the cell samples for the first time due to the use of lyophilization. The conditions of supercritical fluid extraction and supercritical fluid chromatography?quadrupole tandem mass spectrometry were investigated systematically. Under the optimized conditions, all the calibration curves for the lipid mediators showed good linearity (correlation coefficient > 0.99). The limits of detection and the limits of quantification were in the range of 0.190?5.36 pg and 0.560?16.2 pg, respectively. The recoveries were in the range of 70.3?125%. The relative standard deviations of the precision ranged from 1.49?18.7% and the accuracies were higher than 84%. Compared with liquid?liquid extraction coupled with liquid chromatography and tandem mass spectrometry method, the present approach reduced the manual labor and obtained higher sensitivity as well as higher extraction recoveries for all 15 lipid mediators. Finally, the online method was applied to the quantification of lipid mediators in breast cancer cells and normal mammary epithelial cells. On the basis of the results, this lyophilization?supercritical fluid extraction online coupled with supercritical fluid chromatography?quadrupole tandem mass spectrometry method showed great promise in the analysis of lipid mediators in complex biological samples. 相似文献
105.
针对抗肿瘤小分子药物靶向性差、疗效低和毒副性大等缺陷,我们以Y型分子筛(YMS)为基体、阿霉素(DOX)为药物模型,通过pH调控,借助氢键和范德华力等物理作用力制备得到高负载Y型分子筛纳米药物体系(YMS?DOX)。采用UV?Vis、FT?IR、粒径和电位测试及荧光光谱证实YMS?DOX成功制备,且DOX的负载率可高达99.61%。体外药物释放测试发现YMS?DOX具有pH响应释放特性,在肿瘤环境中(pH=4.5)的药物释放量为正常生理环境(pH=7.4)中的3.8倍,表明其具有良好的药物输送特性。此外,利用流式细胞术和MTT测试法探究了YMS?DOX对乳腺癌细胞(MM?231)和树突细胞(DC)的细胞凋亡和毒性,结果表明YMS?DOX可以诱导肿瘤细胞凋亡,且可降低对正常细胞的毒副作用。 相似文献
106.
107.
Stereospecific Nickel‐Catalyzed Cross‐Coupling Reactions of Alkyl Grignard Reagents and Identification of Selective Anti‐Breast‐Cancer Agents 下载免费PDF全文
Ivelina M. Yonova A. George Johnson Charlotte A. Osborne Dr. Curtis E. Moore Prof. Naomi S. Morrissette Prof. Elizabeth R. Jarvo 《Angewandte Chemie (International ed. in English)》2014,53(9):2422-2427
Alkyl Grignard reagents that contain β‐hydrogen atoms were used in a stereospecific nickel‐catalyzed cross‐coupling reaction to form C(sp3)? C(sp3) bonds. Aryl Grignard reagents were also utilized to synthesize 1,1‐diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF‐7 breast cancer cells. 相似文献
108.
《Mendeleev Communications》2023,33(4):469-471
Thz-Phe-D-Trp-Lys-Thr-DOTA, a conjugate of the DOTA chelator and the Thz-Phe-D-Trp-Lys-Thr pentapeptide, was labeled with 152Eu and 161Tb radionuclides, where 161Tb has decay characteristics suitable for its use in cancer therapy. For the [152Eu]Eu-Thz-Phe-D-Trp-Lys-Thr-DOTA complex, the biodistribution in nude mice bearing IMR-32 tumors was evaluated for the first time. It was shown that the complexes of the conjugate demonstrate accumulation in the tumor at the level of DOTA-TATE, another peptide conjugate widely used in nuclear medicine for the diagnosis and therapy of neuroendocrine tumors, which allows Thz-Phe-D-Trp-Lys-Thr-DOTA to be considered as a potential biological vector for radiopharmaceuticals. 相似文献
109.
110.
Hong Zhao Rui Wu Lie‐Feng Ma Li‐Ke Wo Yuan‐Yuan Hu Chao Chen Zha‐Jun Zhan 《Helvetica chimica acta》2016,99(7):543-546
Two new polyene polyketides, namely aurovertins T and U ( 1 and 2 ), were isolated from Calcarisporium arbuscula, together with aurovertins B ( 3 ), D and E ( 4 and 5 ), and M ( 6 ). The structures were elucidated by extensive spectroscopic methods (especially 2D‐NMR techniques). The cytotoxic activities of all isolates against human triple‐negative breast cancer cell line (MDA‐MB‐231) were evaluated. As a result, compounds 3 , 4 , and 6 exhibited more potent cytotoxic activities against MDA‐MB‐231 cell line than the positive control taxol. Also, discussion about the relationships between structure and activity of these aurovertins was presented. 相似文献