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821.
Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.  相似文献   
822.
叙述了七号信令的第4级——电话用户部分(TUP)功能,以及基于DES-3数字程控交换机配置的七号信令系统第4级功能的软件设计及实现,并在H省实现了DES-3数字程控交换机七号信令系统与S1240、E10B七号信令系统的对接。运行结果表明,第4级TUP功能运行稳定,故障率低,大话务呼叫呼损率小于4×10-4,达到了设计要求。  相似文献   
823.
TOR(target of rapamycin)介导的翻译调控   总被引:3,自引:0,他引:3  
TOR是细胞营养状态、能量状态的传感器,其信号转导系统参与了细胞外营养成分、生长因子等对细胞生长的调控,它通过调控蛋白质翻译过程的多个环节,如通过调控S6KI、4E-BPI、eEF2等多种因子的生物功能,从而在蛋白质翻译的起始、延伸等多个水平调控体内蛋白质的翻译,从而影响细胞的生长以及细胞周期的调控。  相似文献   
824.
01地下室送排风系统属于反应堆厂房通风空调系统中的子系统。在中国先进研究堆(CARR)调试阶段运行过程中,发现室外湿热空气进入01地下室各工艺间后,在墙壁及运行设备上凝结大量冷凝水,影响运行设备安全。该文在分析了现场环境条件、设备安装情况下,提出了对01地下室送风系统的技术改造方案,在送风机箱上改装冷冻除湿单元等。经改造后调试试验证实,01地下室湿度明显降低,无大量冷凝水出现,排除了影响设备安全运行的隐患。同时,加装的电加热器也有效解决了,冷冻除湿装置投入后,01地下室工作环境温度较低的问题。  相似文献   
825.
 结直肠癌(CRC)是全球发病率最高的消化道肿瘤之一,严重威胁人类的健康。近年来,类器官技术取得了令人欣喜的进展,已成为结直肠癌发生机制和临床转化研究的重要新工具。回顾了结直肠癌生态位信号通路的变化,总结了类器官技术在结直肠癌建模、肿瘤微环境研究、药物筛选、个体化治疗等方面的应用进展,讨论了当前类器官面临的挑战,并从类器官培养技术标准化和工程技术应用等角度展望了类器官的未来发展方向。  相似文献   
826.
为深入了解木本植物响应干旱胁迫的分子机理,本文系统的从木本植物对干旱信号的感知、信号转导到转录调控、生理生化反应以及表型变化等方面总结了木本植物对干旱胁迫可能的响应过程.认为木本植物由于其固着根生的特点,不得不进化出相应的机制来应对不断变化的环境.当遭受干旱胁迫时,木本植物根系细胞膜上的感受器首先感知到土壤水分状态的变化,细胞内的蛋白质和激素调控系统触发相应的干旱适应反应.干旱信号通过细胞间的信号传导路径传递到植物体内的各个部位,主要的信号传导途径包括Ca2+信号、激素信号和转录因子调控等.一些关键基因和信号通路,如脱落酸(ABA)信号通路、DREB蛋白家族等也参与调控植物的干旱适应性.木本植物也会发生形态和解剖上的变化来减少水分蒸发和增强根系的吸水能力.本文可为抗旱型木本植物选育提供见解.  相似文献   
827.
Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic symmetrical multiple arthritis. Current traditional counter-therapies are expensive and have side effects. Xanthii Fructus has effects in expelling wind and cold, draining the nasal orifice, and removing wind and dampness. However, its mechanism of action against rheumatoid arthritis is unknown. In this paper, the mechanism of the anti- rheumatoid arthritis effect of Xanthii Fructus is studied by proteomics. The experimental results show that it could significantly reduce serum inflammatory factor levels, alleviate joint edema, improve vasodilation and congestion, and significantly reduce the number of inflammatory cells. Proteomics results show that the PI3K-AKT signaling pathway is the key pathway for Xanthii Fructus to treat rheumatoid arthritis. In this study, we obtained a new understanding of the mechanism of Xanthii Fructus in the treatment of rheumatoid arthritis, which provided a theoretical basis for its prevention and treatment and laid the foundation for further research.  相似文献   
828.
Nanoagrochemicals conceived based on safe-by-design principles could provide, besides yield increases, real benefits for the environment due to lower losses of agrochemicals to wind drift and rainwater run-off, and lower toxicity to non-target organisms. As an emerging new technology rather than ‘just another’ active ingredient, nanoagrochemicals should be evaluated and compared to conventional products using multiple criteria, including the production costs, efficiency, mode of action, degradability, and (lack of) effects on non-target organisms. Current studies on nanopesticides suggest, on average, ca. 31 % more efficiency and ca. 43 % less toxicity on non-target organisms. Observations of a 5–10-fold increase in efficiency in laboratory studies need validation in the field. The most significant challenges for nanoagrochemicals today are to produce them at competitive costs and overcome the regulatory obstacles to register products containing nanomaterials.  相似文献   
829.
运用微分方程理论,讨论了具有时滞的不确定性系统的时滞相关稳定条件,给出了系统渐近稳定的时滞界,并给出了系统衰减速率的估值,文末给出的数值例子表明,本文提出的方法所得结果优于现有有关文献的结果.参23  相似文献   
830.
Native reactive electrophilic species (RES) are long-recognized regulators of pathophysiology; yet, knowledge surrounding how RES regulate context-specific biology remains limited. The latest technological advances in profiling and precision decoding of RES sensing and signaling have begun to bring about improved understanding of localized RES regulatory paradigms. However, studies in purified systems — prerequisites for gaining structure/function insights — prove challenging. We here introduce emerging chemical biology tools available to probe RES signaling, and the new knowledge that these tools have brought to the field. We next discuss existing structural data of RES-sensor proteins complexed with electrophilic metabolites or small molecule drugs (limited to <300 Da), including challenges faced in acquiring homogenous RES-bound proteins. We further offer considerations that could promote enhanced understanding of RES regulation derived from three-dimensional structures of RES-modified proteins.  相似文献   
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