全文获取类型
收费全文 | 72513篇 |
免费 | 5043篇 |
国内免费 | 2655篇 |
专业分类
80211篇 |
出版年
2024年 | 139篇 |
2023年 | 1221篇 |
2022年 | 1810篇 |
2021年 | 2416篇 |
2020年 | 2351篇 |
2019年 | 3266篇 |
2018年 | 2841篇 |
2017年 | 2037篇 |
2016年 | 2011篇 |
2015年 | 2515篇 |
2014年 | 4743篇 |
2013年 | 5894篇 |
2012年 | 3653篇 |
2011年 | 4693篇 |
2010年 | 3573篇 |
2009年 | 3871篇 |
2008年 | 3940篇 |
2007年 | 3967篇 |
2006年 | 3519篇 |
2005年 | 3053篇 |
2004年 | 2703篇 |
2003年 | 2147篇 |
2002年 | 1927篇 |
2001年 | 1228篇 |
2000年 | 951篇 |
1999年 | 972篇 |
1998年 | 976篇 |
1997年 | 764篇 |
1996年 | 684篇 |
1995年 | 613篇 |
1994年 | 565篇 |
1993年 | 431篇 |
1992年 | 432篇 |
1991年 | 356篇 |
1990年 | 293篇 |
1989年 | 241篇 |
1988年 | 211篇 |
1987年 | 184篇 |
1986年 | 161篇 |
1985年 | 272篇 |
1984年 | 455篇 |
1983年 | 336篇 |
1982年 | 347篇 |
1981年 | 264篇 |
1980年 | 201篇 |
1979年 | 194篇 |
1978年 | 172篇 |
1977年 | 143篇 |
1976年 | 115篇 |
1975年 | 108篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
981.
Mohammed S. Taghour Hazem Elkady Wagdy M. Eldehna Nehal M. El-Deeb Ahmed M. Kenawy Eslam B. Elkaeed Aisha A. Alsfouk Mohamed S. Alesawy Ahmed M. Metwaly Ibrahim. H. Eissa 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1903
A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 µM, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2. 相似文献
982.
The centrosome linker component C‐Nap1 (encoded by CEP250) anchors filaments to centrioles that provide centrosome cohesion by connecting the two centrosomes of an interphase cell into a single microtubule organizing unit. The role of the centrosome linker during development of an animal remains enigmatic. Here, we show that male CEP250 −/− mice are sterile because sperm production is abolished. Premature centrosome separation means that germ stem cells in CEP250 −/− mice fail to establish an E‐cadherin polarity mark and are unable to maintain the older mother centrosome on the basal site of the seminiferous tubules. This failure prompts premature stem cell differentiation in expense of germ stem cell expansion. The concomitant induction of apoptosis triggers the complete depletion of germ stem cells and consequently infertility. Our study reveals a role for centrosome cohesion in asymmetric cell division, stem cell maintenance, and fertility. 相似文献
983.
Yiwen Liu Jianfang Gao Min Xu Qianqian Zhou Zhongxiao Zhang Jiaxin Ye Rui Li 《Journal of cellular and molecular medicine》2022,26(13):3616
Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non‐coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ‐RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ‐RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial‐specific markers CTnT, Mef2c, and GATA4. Next, we found that circ‐RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ‐RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ‐RCCD inhibited nuclear translocation of YY1. These results reported that circ‐RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ‐RCCD as a target for the treatment of CHD. 相似文献
984.
985.
986.
Samil Jung Davaajargal Myagmarjav Taeyeon Jo Soonduk Lee Songyi Han Nguyen Thi Ngoc Quynh Nguyen Hai Anh Son Hai Vu Yeongseon Choi Myeong-Sok Lee 《International journal of biological sciences》2022,18(9):3859
Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival. 相似文献
987.
988.
高温强光对温州蜜柑叶绿素荧光、D1蛋白和Deg1蛋白酶的影响及SA效应 总被引:1,自引:0,他引:1
以3年生温州蜜柑(Citrus unishiu Marc.)植株为试材,用叶绿素荧光分析、Western-blotting蛋白质印记技术及DAB(3,3'-二氨基联苯胺)显色法,研究了高温强光(38℃和1600 μmol?m-2?s-1)对叶片叶绿素荧光参数、PS(光系统)II反应中心D1蛋白和Deg1蛋白酶的影响和SA(水杨酸)的效应。结果表明,高温强光交互作用4 h后,叶片的初始荧光Fo升高,最大光能转化效率Fv/Fm、表观光合电子传递速率ETR及PSII的量子产额ΦPSII显著降低,在D1蛋白降解的同时,Deg1蛋白酶含量也下降,并伴有H2O2的积累。在高温强光下,外源的H2O2使叶绿素荧光动力学快相参数(Fi-Fo)/(Fp-Fo)值(反映PSII中QB非还原中心的数量)升高和I-P的斜率(反映PSII 活化中心还原态QA积累的值)下降,Fv/Fm、ETR、ΦPSII及D1蛋白和Deg1蛋白酶下降幅度增大;而外源的SA使这些参数下降幅度减小。这些结果说明,高温强光诱导H2O2的积累造成Deg1蛋白酶和光系统反应中心D1蛋白的降解,Deg1蛋白酶的减少也进一步限制了D1蛋白的周转,进而使温州蜜柑PSII反应中心遭到破坏,SA对光合机构光破坏有保护作用。 相似文献
989.
褐菖鲉肝CYP 1A作为生物标志物监测厦门海域石油污染状况 总被引:2,自引:0,他引:2
以褐菖鲉为实验鱼类,以鱼肝微粒体CYP1A 生物标志物(EROD活性和CYP1A蛋白表达量)为指标,在厦门海域开展了两次野外监测实验,研究EROD活性和CYP1A蛋白表达量的变化,以及它们与海水和沉积物中石油类和重金属含量之间的相关性。结果表明,在现场属于一类海水的石油类浓度(0.0121-0.0242 mg/L)条件下,石油类就能够显著诱导褐菖鲉肝EROD活性和CYP1A蛋白表达量,鱼肝EROD活性和CYP1A蛋白表达量与海水中石油类含量均呈现极显著正相关,CYP1A蛋白表达量比EROD活性较为敏感和稳定。此外,在监测实验中,尚未发现这两种生物标志物受所监测海区的海水和沉积物重金属含量的影响。因此,利用褐菖鲉肝微粒体EROD活性和CYP1A蛋白表达量作为生物标志物监测海洋石油类及其PAHs污染是可行的,在海洋环境石油类污染监测及其生化效应评价中具有重要的应用价值。而且,把这两种生物标志物结合起来加以研究并推广应用将更有意义。 相似文献
990.
该研究探讨了长链非编码RNA KCNQ1OT1对脂多糖(LPS)诱导的血管内皮细胞(VEC)凋亡和炎性因子表达的影响以及其可能机制.通过体外培养VEC,分别转染KCNQ1OT1过表达载体、miR-223抑制剂或共转染KCNQ1OT1过表达载体与miR-223模拟物后,用1.0mg/mLLPS干预24h,然后采用RT-q... 相似文献