全文获取类型
收费全文 | 84篇 |
免费 | 21篇 |
国内免费 | 10篇 |
专业分类
化学 | 108篇 |
物理学 | 7篇 |
出版年
2023年 | 3篇 |
2021年 | 15篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 3篇 |
2012年 | 3篇 |
2011年 | 2篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
排序方式: 共有115条查询结果,搜索用时 31 毫秒
31.
VinayKumar Dachuri Phil Hyun Song Young Woo Kim Sae-Kwang Ku Chang-Hyun Song 《Molecules (Basel, Switzerland)》2020,25(23)
Acute kidney injury (AKI) is a disease caused by sudden renal dysfunction, which is an important risk factor for chronic renal failure. However, there is no effective treatment for renal impairment. Although some traditional polyherbs are commercially available for renal diseases, their effectiveness has not been reported. Therefore, we examined the nephroprotective effects of polyherbs and their relevant mechanisms in a cisplatin-induced cell injury model. Rat NRK-52E and human HK-2 subjected to cisplatin-induced AKI were treated with four polyherbs, Injinhotang (IJ), Ucha-Shinki-Hwan (US), Yukmijihwang-tang (YJ), and UrofenTM (Uro) similar with Yondansagan-tang, for three days. All polyherbs showed strong free radical scavenging activities, and the treatments prevented cisplatin-induced cell death in both models, especially at 1.2 mg/mL. The protective effects involved antioxidant effects by reducing reactive oxygen species and increasing the activities of superoxide dismutase and catalase. The polyherbs also reduced the number of annexin V-positive apoptotic cells and the expression of cleaved caspase-3, along with inhibited expression of mitogen-activated protein kinase-related proteins. These findings provide evidence for promoting the development of herbal formulas as an alternative therapy for treating AKI. 相似文献
32.
Dr. Rakesh K. Pathak Christopher D. McNitt Prof. Dr. Vladimir V. Popik Prof. Dr. Shanta Dhar 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(23):6861-6865
The ability to rationally design and construct a platform technology to develop new platinum(IV) [PtIV] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well‐defined chemistry is critical for discovering new platinum‐based therapeutics. With limited numbers of possibilities considering the sensitivity of PtIV centers, we used a strain‐promoted azide–alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single PtIV precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated. 相似文献
33.
Enzyme‐Instructed Intracellular Molecular Self‐Assembly to Boost Activity of Cisplatin against Drug‐Resistant Ovarian Cancer Cells 下载免费PDF全文
Jie Li Yi Kuang Junfeng Shi Jie Zhou Jamie E. Medina Rong Zhou Dan Yuan Cuihong Yang Huaimin Wang Prof. Zhimou Yang Prof. Jianfeng Liu Prof. Dr. Daniela M. Dinulescu Prof. Dr. Bing Xu 《Angewandte Chemie (International ed. in English)》2015,54(45):13307-13311
Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug‐resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme‐instructed self‐assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug‐resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre‐installed on the precursors to form the peptides that self‐assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug‐resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non‐cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects. 相似文献
34.
Dr. Shuai Jiang Ming Xiao Prof. Wen Sun Dr. Daniel Crespy Prof. Volker Mailänder Prof. Xiaojun Peng Prof. Jiangli Fan Prof. Dr. Katharina Landfester 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(45):20183-20191
The anticancer efficacy of photodynamic therapy (PDT) is limited due to the hypoxic features of solid tumors. We report synergistic PDT/chemotherapy with integrated tandem Fenton reactions mediated by ovalbumin encapsulation for improved in vivo anticancer therapy via an enhanced reactive oxygen species (ROS) generation mechanism. O2.− produced by the PDT is converted to H2O2 by superoxide dismutase, followed by the transformation of H2O2 to the highly toxic .OH via Fenton reactions by Fe2+ originating from the dissolution of co-loaded Fe3O4 nanoparticles. The PDT process further facilitates the endosomal/lysosomal escape of the active agents and enhances their intracellular delivery to the nucleus—even for drug-resistant cells. Cisplatin generates O2.− in the presence of nicotinamide adenine dinucleotide phosphate oxidase and thereby improves the treatment efficiency by serving as an additional O2.− source for production of .OH radicals. Improved anticancer efficiency is achieved under both hypoxic and normoxic conditions. 相似文献
35.
Elisabetta Gabano Giulia Pinton Cecilia Balzano Sara Boumya Domenico Osella Laura Moro Mauro Ravera 《Molecules (Basel, Switzerland)》2021,26(16)
Cisplatin is widely employed as a first-line chemotherapeutic agent for many solid tumors, including malignant pleural mesothelioma (MPM). However, its clinical use is limited by heavy side effects and acquired resistance, the latter being mainly related to enhanced DNA repair. Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPis) have been carried out, with the hope that such combinations might lead to improved therapeutic efficacy against tumors. Here, the synthesis and efficacy in reducing MPM cell viability of four cisplatin-based Pt(IV) prodrugs containing the PARPi 3-aminobenzamide (3-ABA) fragment are described. The most promising conjugate is more effective than cisplatin or cisplatin/3-ABA combination, administered in equimolar doses, in inhibiting PARP-1 activity and inducing apoptosis in BRCA1/2 wild type MPM cells, grown as monolayer or as multicellular spheroids. 相似文献
36.
摘要 目的 以甘草查尔酮母核为先导化合物骨架,设计、合成一系列新型咪唑-查尔酮衍生物并进行抗宫颈癌活性研究。方法 在查尔酮骨架的B环引入4种咪唑环,在A环分别引入甲氧基、氨基、羟基等活性基团;采用Claisen-Schmidt反应合成系列新型咪唑-查尔酮衍生物,其结构经1H-NMR、13C-NMR和HRMS进行表征。通过MTT、Transwell、流式细胞仪和分子对接实验方法,初步探索目标化合物的抗宫颈癌活性及作用机制。结果 大部分化合物具有一定的抗宫颈癌活性,其中2i较为显著,且对正常细胞的毒性较小。此外,化合物2i能够显著抑制HeLa和HeLa/DDP细胞的迁移和侵袭能力,能够诱导其凋亡,并阻滞HeLa和HeLa/DDP细胞于G2/M期;分子对接模拟显示2i与查尔酮母核和原配体秋水仙碱相比,2i与微管蛋白秋水仙碱结合位点具有较好的结合能力,并能够产生氢键相互作用力。结论 化合物2i具有较显著的抗宫颈癌和抗宫颈癌顺铂耐药活性作用,这可能与其抑制了微管蛋白靶点有关。 相似文献
37.
38.
The investigation of the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers is of special relevance to unveil the mechanisms involved in different steps of the anticancer mode of action of these drugs. We have simulated the permeation of cisplatin through a model membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids by means of umbrella sampling classical molecular dynamics simulations. The initial physisorption of cisplatin into the polar region of the lipid membrane is controlled by long-range electrostatic interactions with the choline groups in a first step and, in a second step, by long-range electrostatic and hydrogen bond interactions with the phosphate groups. The second half of the permeation pathway, in which cisplatin diffuses through the nonpolar region of the bilayer, is characterized by the drop of the interactions with the polar heads and the rise of attractive interactions with the non-polar tails, which are dominated by van der Waals contributions. The permeation free-energy profile is explained by a complex balance between the drug/lipid interactions and the energy and entropy contributions associated with the dehydration of the drug along the permeation pathway and with the decrease and increase of the membrane ordering along the first and second half of the mechanism, respectively. 相似文献
39.
Alessandra Barbanente Rosa Maria Iacobazzi Amalia Azzariti James D. Hoeschele Nunzio Denora Paride Papadia Concetta Pacifico Giovanni Natile Nicola Margiotta 《Molecules (Basel, Switzerland)》2021,26(11)
Two new Pt(II)-pyrophosphato complexes containing the carrier ligands cis-1,3-diaminocyclohexane (cis-1,3-DACH) and trans-1,2-diamine-4-cyclohexene (1,2-DACHEX), variants of the 1R,2R-diaminocyclohexane ligand present in the clinically used Pt-drug oxaliplatin, have been synthesized with the aim of developing new potential antitumor drugs with high bone tropism. The complexes are more stable at physiological pH than in acid conditions, with Na2[Pt(pyrophosphato)(cis-1,3-DACH)] (1) slightly more stable than [Pt(dihydrogenpyrophosphato)(1,2-DACHEX)] (2). The greater reactivity at acidic pH ensures a greater efficacy at the tumor site. Preliminary NMR studies indicate that 1 and 2 react slowly with 5’-GMP (used as a model of nucleic acids), releasing the pyrophosphate ligand and affording the bis 5’-GMP adduct. In vitro cytotoxicity assays performed against a panel of four human cancer cell lines have shown that both compounds are more active than oxaliplatin. Flow cytometry studies on HCT116 cells showed that the pyrophosphato compounds with the non-classical 1,3- and 1,4-diaminocyclohexane ligands (1 and 4) are the most capable to induce cells’ death by apoptosis and necrosis. 相似文献
40.
通过逐步沉淀反应一锅法制备了一系列不同含量的镁掺杂纳米羟基磷灰石。通过硝酸镁、硝酸钙不同的投料物质的量比调控纳米颗粒的形态和尺寸。通过透射电子显微镜(TEM)、X射线衍射(XRD)等分析手段对镁掺杂纳米羟基磷灰石进行物理化学性能表征,用MTT法评价其体外细胞毒性。研究结果表明:镁掺杂纳米羟基磷灰石呈现束状纳米纤维形态、比表面积大、细胞毒性较低;将其作为载体负载抗癌药物顺铂,具有很好的载药能力,载药量可达54%,该载药纳米颗粒还具备缓释特性(72 h释药量达到41.72%)和很好抑制癌细胞生长的效果。 相似文献