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71.
Two novel unsymmetrical Ir(III) complexes [Ir(ppy)2(N N)Cl2] (N N=2-(pyrazin-2-yl)naphtha[1,2-e][1,2,4]triazine, Ir1 ; 2-(pyrazin-2-yl)-4b,4b’-dihydroaceanthryleno[1,2-e][1,2,4]triazine, Ir2 ) were developed as chemotherapy agents. Ir1 was mainly located in mitochondria. In contrast, Ir2 accumulated in mitochondria but subsequently migrated to the nucleus. Ir1 and Ir2 showed cytotoxicity toward cancerous cells, especially the cisplatin-resistant ones, indicating their ability to overcome cisplatin resistance. Although both Ir1 and Ir2 disrupted mitochondrial metabolism, they showed different cell death mechanisms. Ir1 induced mitochondria-mediated apoptosis in cisplatin-resistant A549R cells. Ir2 was demonstrated to cause PARP-1 activated necroptosis in A549R cells. This study provides an experimental basis for the rational design of metal-based chemotherapeutic drugs.  相似文献   
72.
With the continuous updating of cancer treatment methods and the rapid development of precision medicine in recent years, there are higher demands for advanced and versatile drug delivery systems. Scientists are committed to create greener and more effective nanomedicines where the carrier is no longer limited to a single function of drug delivery. Polyphenols, which can act as both active ingredients and fundamental building blocks, are being explored as potential multifunctional carriers that are efficient and safe for design purposes. Due to their intrinsic anticancer activity, phenolic compounds have shown surprising expressiveness in ablation of tumor cells, overcoming cancer multidrug resistance (MDR), and enhancing immunotherapeutic efficacy. This review provides an overview of recent advances in the design, synthesis, and application of versatile polyphenol-based nanosystems for cancer therapy in various modes. Moreover, the merits of polyphenols and the challenges for their clinical translation are also discussed, and it is pointed out that the novel polyphenol delivery system requires further optimization and validation.  相似文献   
73.
Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.  相似文献   
74.
Modern phytotherapy is part of today’s conventional evidence-based medicine and the use of phytopharmaceuticals in integrative oncology is becoming increasingly popular. Approximately 40% of users of such phytopharmaceuticals are tumour patients. The present review provides an overview of the most important plants and nature-based compounds used in integrative oncology and illustrates their pharmacological potential in preclinical and clinical settings. A selection of promising anti-tumour plants and ingredients was made on the basis of scientific evidence and therapeutic practical relevance and included Boswellia, gingko, ginseng, ginger, and curcumin. In addition to these nominees, there is a large number of other interesting plants and plant ingredients that can be considered for the treatment of cancer diseases or for the treatment of tumour or tumour therapy-associated symptoms. Side effects and interactions are included in the discussion. However, with the regular and intended use of phytopharmaceuticals, the occurrence of adverse side effects is rather rare. Overall, the use of defined phytopharmaceuticals is recommended in the context of a rational integrative oncology approach.  相似文献   
75.
以中草药有效成分β-榄香烯为起始原料, 经烯丙位的氯代反应及亲核取代反应在β-榄香烯母体上成功地引入含吡啶基的三齿螯合剂, 并与稳定的三羰基铼配位, 得到了一种新的铼(I)三齿配合物, 在此基础上利用铼的放射性同位素Re-188进行了放射性标记. 反应中间体及最终化合物分别用IR, 1H NMR, HRMS, HPLC或元素分析进行表征, 并对该化合物进行了初步的体外抗癌活性研究. β-榄香烯三羰基铼配合物的合成、放射化学合成及体外抗癌活性评价, 为探讨β-榄香烯体内靶点和作用机制提供了可能, 并为最终开发基于β-榄香烯的放射性药物奠定了基础.  相似文献   
76.
王兰  周微  张广明  赵广荣 《合成化学》2007,15(5):608-611
以3,4-二氢-3-甲基-4-氧代咪唑[5,1-d]并[1,2,3,5]四嗪-8-甲酰胺和苯磺酰基呋咱氮氧化物为原料,通过肖滕-鲍曼法合成了5种新的咪唑四嗪衍生物——3,4-二氢-3-甲基-4-氧代咪唑[5,1-d]并[1,2,3,5]四嗪-8-甲酸苯磺酰基呋咱氮氧基酯,其结构经1H NMR,IR,MS和元素分析确证。  相似文献   
77.
A liquid chromatographic/tandem mass spectrometric method was developed and validated for the quantitation of capecitabine and its metabolite 5-fluorouracil in human plasma. The simultaneous determination of both analytes was achieved by a column switching method using a trapping column and two analytical columns with different stationary phases. Isocratic elution was used for the separation of capecitabine on a C18 column whereas 5-fluorouracil was separated using gradient elution on an non-polar carbon phase. The calibration curves were linear for both compounds with a correlation factor (R2) > 0.9993 for 5-fluorouracil and >0.9942 for capecitabine. The assay was validated in the concentration range 5.00-1000 ng ml(-1) for both compounds. The intra-day precision was better than 10% for 5-fluorouracil and better than 11% for capecitabine whereas the inter-day precision was better than 8% for 5-fluorouracil and better than 14% for capecitabine.  相似文献   
78.
Telomeric DNA represents a novel target for the development of anticancer drugs. By application of a catalytic metallodrug strategy, a copper–acridine–ATCUN complex (CuGGHK‐Acr) has been designed that targets G‐quadruplex telomeric DNA. Both fluorescence solution assays and gel sequencing demonstrate the CuGGHK‐Acr catalyst to selectively bind and cleave the G‐quadruplex telomere sequence. The cleavage pathway has been mapped by matrix assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) experiments. CuGGHK‐Acr promotes significant inhibition of cancer cell proliferation and shortening of telomere length. Both senescence and apoptosis are induced in the breast cancer cell line MCF7.  相似文献   
79.
A mild and efficient one‐pot method has been developed for the stereoselective synthesis of structurally diverse novel iminosugar C‐alkynylglycosides. The generality of this methodology has been demonstrated with a wide variety of amines and copper acetylides. This one‐pot method has been exploited in the synthesis of new class of DNA cross‐linking agents, polyhydroxy 1‐vinyl‐tetrahydroindolizine derivatives.  相似文献   
80.
基于24个目前已知的氧肟酸类组蛋白去乙酰化酶抑制剂,我们运用Catalyst软件建立了一个三维药效团模型。其中,最好的药效团模型1,包含了四个化学特征(一个氢键供体,一个芳环和两个疏水基),相关系数达到0.946,并由另外20个化合物进行了测试验证。我们第一次特征性描述了组蛋白去乙酰化酶的帽子(CAP)部分。我们的研究结果对于设计全新组蛋白去乙酰化酶抑制剂具有很好的指导作用。  相似文献   
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