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It had been found that interleukin-8 (IL-8) was associated with drug resistance. We previously demonstrated that the resistance to 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) of glioma cell line SWOZI was much higher than that of cell line SOWZ2, which were both cloned from the same parental glioma cell line SWO38. In this study, IL-8 was found to be upregulated both in SWOZ1 and SWOZ2-BCNU, a BCNU-resistant glioma cell line. To further investigate the function of IL-8, the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU were treated with siRNAs targeting IL-8. The results of quantitative RT-PCR showed that a decreased level of IL-8 mRNA expression in SWOZI and SWOZ2-BCNU for more than 90% compared to negative control and was confirmed by western blot assay (P 〈 0.05) after treated by siRNAs targeting IL-8. Subsequently, the cytotoxicity of BCNU to these cell lines was detected using the cell counting kit-8 assay. As a result, the BCNU resistance was reversed for about 50% both in these two cell lines (P 〈 0.05). Our data demonstrated that inhibition of IL-8 with specific siRNAs can reverse the BCNU resistant phenotype in glioma cell lines, indicating that IL-8 may play an important role in BCNU-resistance in glioma. 相似文献
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《Expert opinion on drug delivery》2013,10(4):639-651
RNA interference is becoming the technique of choice for analysing gene function and drug target validation. In this process, sequence-specific gene inhibition is initiated by small RNA duplexes, known as small interfering RNAs (siRNAs). The possibility that exogenously delivered siRNAs or endogenously expressed hairpin siRNAs can cause the destruction of specific target mRNA in vitro and in animal models has been demonstrated. However, the key challenges for the development of siRNAs as human therapeutics is largely dependent on the development of suitable delivery agents and improved siRNA specificity. This review highlights recent advances in siRNA delivery, as well as challenging problems related to immune stimulation. 相似文献
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《Expert opinion on drug discovery》2013,8(6):889-903
This is a review of RNA as a target for small molecules (ribosomes, riboswitches, regulatory RNAs) and RNA-derived oligonucleotides as tools (antisense/small interfering RNA, ribozymes, aptamers/decoy RNA and microRNA). This review highlights the present state of research using RNA as a drug target or as a potential drug candidate and explains at which stage and to what extent rational design could eventually be involved. Special attention has been paid to the recent potential clinical applications of RNA either as drugs or drug targets. The review deals mainly with mechanistic approaches rather than with physicochemical or computational aspects of RNA-based drug design. 相似文献
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目的构建smad2特异性小干扰RNA(siRNA)真核表达载体,并检测肿瘤细胞中其对smad2基因表达的干扰效果。方法根据smad2基因序列设计合理的smad2 siRNA,并将合成的寡核苷酸序列克隆到pSliencer 2.1-U6 neo载体中,转化大肠杆菌DH5α;挑取阳性菌落进行质粒酶切和序列分析;将构建正确的smad2 siRNA重组质粒转染,或与带Flag标签的smads真核表达载体共同转染293T细胞或HeLa细胞,收集细胞裂解物,Westem印迹检测siRNA的干扰效果。结果正确构建了smad2 siRNA重组质粒,对smad2表达的特异性干扰效果可达70%以上。结论成功构建了smad2 siRNA载体,为进一步探讨smad2在肿瘤发生发展中的作用奠定了基础。 相似文献
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Jay S. Petrick Brent Brower-Toland Aimee L. Jackson Larry D. Kier 《Regulatory toxicology and pharmacology : RTP》2013
Gene expression can be modulated in plants to produce desired traits through agricultural biotechnology. Currently, biotechnology-derived crops are compared to their conventional counterparts, with safety assessments conducted on the genetic modification and the intended and unintended differences. This review proposes that this comparative safety assessment paradigm is appropriate for plants modified to express mediators of RNA-mediated gene regulation, including RNA interference (RNAi), a gene suppression mechanism that naturally occurs in plants and animals. The molecular mediators of RNAi, including long double-stranded RNAs (dsRNA), small interfering RNAs (siRNA), and microRNAs (miRNA), occur naturally in foods; therefore, there is an extensive history of safe consumption. Systemic exposure following consumption of plants containing dsRNAs that mediate RNAi is limited in higher organisms by extensive degradation of ingested nucleic acids and by biological barriers to uptake and efficacy of exogenous nucleic acids. A number of mammalian RNAi studies support the concept that a large margin of safety will exist for any small fraction of RNAs that might be absorbed following consumption of foods from biotechnology-derived plants that employ RNA-mediated gene regulation. Food and feed derived from these crops utilizing RNA-based mechanisms is therefore expected to be as safe as food and feed derived through conventional plant breeding. 相似文献
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Boukerche H Su ZZ Prévot C Sarkar D Fisher PB 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(41):15914-15919
The scaffold PDZ-domain containing protein mda-9/syntenin functions as a positive regulator of cancer cell progression in human melanoma and other tumors. mda-9/Syntenin regulates cell motility and invasion by altering defined biochemical and signaling pathways, including focal adhesion kinase (FAK), p38 mitogen-activated protein kinase (MAPK) and NF-κB, but precisely how mda-9/syntenin organizes these multiprotein signaling complexes is not well understood. Using a clinically relevant human melanoma model, we demonstrate that mda-9/syntenin physically interacts with c-Src and this communication correlates with an increase in FAK/c-Src complex formation and c-Src activation. Inhibiting mda-9/syntenin, using an adenovirus expressing antisense mda-9/syntenin or addition of c-Src siRNA, suppresses melanoma cell migration, anchorage-independent growth, and spontaneous tumor cell dissemination in vivo in a human melanoma animal metastasis model. These data are compatible with a model wherein interaction of MDA-9/syntenin with c-Src promotes the formation of an active FAK/c-Src signaling complex, leading to enhanced tumor cell invasion and metastatic spread. These provocative findings highlight mda-9/syntenin and its interacting partners as promising therapeutic targets for intervention of metastasis. 相似文献
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Xiao-ke Ji Yuan-kang Xie Jun-qiao Zhong Qi-gang Xu Qi-qiang Zeng Yang Wang Qi-yu Zhang Yun-feng Shan 《Acta pharmacologica Sinica》2015,36(3):334-342