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11.
《Bioorganic & medicinal chemistry》2016,24(2):294-303
New cyclic RGD peptide-anticancer agent conjugates, with different chemical functionalities attached to the parent peptide were synthesized in order to evaluate their biological activities and to provide a comparative study of their drug release profiles. The Integrin binding c(RGDfK) penta-peptide was used for the synthesis of Camptothecin (CPT) carbamate and Chlorambucil (CLB) amide conjugates. Substitution of the amino acid Lys with Ser resulted in a modified c(RGDfS) with a new attachment site, which enabled the synthesis of an ester CLB conjugate. Functional versatility of the conjugates was reflected in the variability of their drug release profiles, while the conserved RGD sequence of a selective binding to the αv integrin family, likely preserved their recognition by the Integrin and consequently their favorable toxicity towards targeted cancer cells. This hypothesis was supported by a computational analysis suggesting that all conjugates occupy conformational spaces similar to that of the Integrin bound bio-active parent peptide. 相似文献
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摘要 目的:探讨肺癌合并肺部感染患者病原菌分布、耐药性分析及血清炎性因子检测的临床意义。方法:选取我院于2018年6月~2020年3月期间收治的肺癌合并肺部感染患者90例为感染组,选取同期我院收治的肺癌未合并肺部感染患者100例为肺癌组,选取同期于我院进行体检的健康志愿者60例为对照组,对肺癌合并肺部感染患者的感染病原菌类型进行总结分析,分析常见病原菌药敏试验结果,统计病原菌耐药率。对比三组受试者的炎性因子水平。结果:90例肺癌合并肺部感染患者的送检痰液标本共检出100株病原菌,100株病原菌中以革兰阴性菌为主,其次为革兰阳性菌、真菌,分别占比63.00%、22.00%、15.00%。肺炎克雷伯菌、鲍氏不动杆菌、铜绿假单胞菌对亚胺培南的耐药率较低,对氨苄西林、甲氨苄啶的耐药率均较高。凝固酶阴性葡萄球菌、金黄色葡萄球菌对万古霉素的耐药率较高,对左氧氟沙星的耐药率较低。白色念珠菌、热带念珠菌对两性霉素B、氟康唑、酮康唑、伊曲康唑的耐药率均较低。感染组、肺癌组的血清白介素-6(IL-6)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)水平均高于对照组,且感染组以上指标水平高于肺癌组(P<0.05)。结论:肺癌合并肺部感染患者体内病原菌种类繁多,对常见抗菌药物的耐药性存在差异,且患者体内存在较强的炎性反应,临床应根据药敏结果合理应用抗菌药物 。 相似文献
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ABSTRACT:?Paclitaxel is a widely used anti-cancer agent. Conjugates of paclitaxel with poly(glutamic acid) have shown great promise in preclinical trials, and clinical trials are now underway. Preclinical data suggest that more paclitaxel is preferentially delivered to tumor sites vs. nonconjugated paclitaxel. When poly(glutamic acid) is conjugated to other families of cancer drugs, similar improvements in effectiveness and reduced toxicity are observed. Optimization of poly(glutamic acid) for use in drug delivery applications is a key step in making this technology viable. 相似文献
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《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):837-839
Abstract Some diacid biodegradable synthesis of aziduthymidine (AZT) were synthesized and applied to production of about 60 different derivatives. 相似文献
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Rebecca Pastrana-Mena Rhoel R. Dinglasan Blandine Franke-Fayard Joel Vega-Rodr��guez Mariela Fuentes-Caraballo Abel Baerga-Ortiz Isabelle Coppens Marcelo Jacobs-Lorena Chris J. Janse Adelfa E. Serrano 《The Journal of biological chemistry》2010,285(35):27045-27056
Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a γ-glutamylcysteine synthetase (γ-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for γ-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and γ-GCS by simultaneous disruption of gr and γ-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism. 相似文献
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Ruth Duncan Pavla Rejmanova Jindrich Kopeček John B. Lloyd 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(1):143-150
Synthetic 125I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [125I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition. 相似文献