全文获取类型
收费全文 | 65716篇 |
免费 | 4446篇 |
国内免费 | 2808篇 |
出版年
2023年 | 1062篇 |
2022年 | 1072篇 |
2021年 | 2088篇 |
2020年 | 2050篇 |
2019年 | 2778篇 |
2018年 | 2470篇 |
2017年 | 1638篇 |
2016年 | 1767篇 |
2015年 | 2208篇 |
2014年 | 3731篇 |
2013年 | 4847篇 |
2012年 | 2719篇 |
2011年 | 3554篇 |
2010年 | 2585篇 |
2009年 | 2941篇 |
2008年 | 3008篇 |
2007年 | 3131篇 |
2006年 | 2769篇 |
2005年 | 2561篇 |
2004年 | 2275篇 |
2003年 | 1961篇 |
2002年 | 1838篇 |
2001年 | 1432篇 |
2000年 | 1240篇 |
1999年 | 1199篇 |
1998年 | 1079篇 |
1997年 | 971篇 |
1996年 | 936篇 |
1995年 | 873篇 |
1994年 | 821篇 |
1993年 | 767篇 |
1992年 | 722篇 |
1991年 | 673篇 |
1990年 | 526篇 |
1989年 | 511篇 |
1988年 | 462篇 |
1987年 | 392篇 |
1986年 | 345篇 |
1985年 | 501篇 |
1984年 | 745篇 |
1983年 | 505篇 |
1982年 | 578篇 |
1981年 | 501篇 |
1980年 | 406篇 |
1979年 | 370篇 |
1978年 | 282篇 |
1977年 | 239篇 |
1976年 | 231篇 |
1974年 | 135篇 |
1973年 | 152篇 |
排序方式: 共有10000条查询结果,搜索用时 265 毫秒
31.
32.
Satoko Iwahori Daisuke Kohmon Junya Kobayashi Yuhei Tani Takashi Yugawa Kenshi Komatsu 《Cell cycle (Georgetown, Tex.)》2014,13(3):471-481
Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. 相似文献
33.
《Journal of molecular biology》2021,433(17):166665
Transient receptor potential melastatin 4 (TRPM4) is a broadly expressed Ca2+ activated monovalent cation channel that contributes to the pathophysiology of several diseases.For this study, we generated stable CRISPR/Cas9 TRPM4 knockout (K.O.) cells from the human prostate cancer cell line DU145 and analyzed the cells for changes in cancer hallmark functions. Both TRPM4-K.O. clones demonstrated lower proliferation and viability compared to the parental cells. Migration was also impaired in the TRPM4-K.O. cells. Additionally, analysis of 210 prostate cancer patient tissues demonstrates a positive association between TRPM4 protein expression and local/metastatic progression. Moreover, a decreased adhesion rate was detected in the two K.O. clones compared to DU145 cells.Next, we tested three novel TRPM4 inhibitors with whole-cell patch clamp technique for their potential to block TRPM4 currents. CBA, NBA and LBA partially inhibited TRPM4 currents in DU145 cells. However, none of these inhibitors demonstrated any TRPM4-specific effect in the cellular assays.To evaluate if the observed effect of TRPM4 K.O. on migration, viability, and cell cycle is linked to TRPM4 ion conductivity, we transfected TRPM4-K.O. cells with either TRPM4 wild-type or a dominant-negative mutant, non-permeable to Na+. Our data showed a partial rescue of the viability of cells expressing functional TRPM4, while the pore mutant was not able to rescue this phenotype. For cell cycle distribution, TRPM4 ion conductivity was not essential since TRPM4 wild-type and the pore mutant rescued the phenotype.In conclusion, TRPM4 contributes to viability, migration, cell cycle shift, and adhesion; however, blocking TRPM4 ion conductivity is insufficient to prevent its role in cancer hallmark functions in prostate cancer cells. 相似文献
34.
《Cell》2021,184(22):5670-5685.e23
35.
《Cell》2021,184(25):6138-6156.e28
36.
37.
Antonis E. Koromilas 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):644-649
Cells employ pro-survival and pro-adaptive pathways to cope with different forms of environmental stress. When stress is excessive, and the damage caused by it is unsustainable, cells engage pro-death pathways, which are in place to protect the host from the deleterious effects of harmed cells. Two important pathways that determine the balance between survival and death of stressed cells are the integrated stress response (ISR) and the mammalian target of rapamycin (mTOR), both of which converge at the level of mRNA translation. The two pathways have established avenues of communication to control their activity and determine the fate of stressed cells in a context-dependent manner. The functional interplay between the ISR and mTOR may have significant ramifications in the development and treatment of human diseases such as diabetes, neurodegeneration and cancer. 相似文献
38.
Cell division in cell suspension cultures can be completely blocked by the growth retardant tetcyclacis at a concentration of 10-4 mol l-1. In rice cells it has been demonstrated that the growth inhibition can be completely overcome by application of cholesterol independent of the duration of pretreatment with tetcyclacis. In suspension cultures of maize and soybean, too, the effect of tetcyclacis on cell division was neutralized by adding cholesterol. Other plant sterols, stigmasterol, campesterol and sitosterol were active in a decreasing order. Modifications in the cholesterol perhydro-cyclopentanophenanthrene-ring system indicate that the hydroxyl group at C-3 and the double bond between C-5 and C-6 in ring B are required for the activity. In contrast, gibberellic acid as well as ent-kaurenoic acid could not compensate retardant effects. Likewise, tetcyclasis did not change the level of gibberellins in rice cells as shown by radioimmunoassay. Thus, it is concluded that in cell suspension cultures sterols play a more important role in cell division than gibberellins.Abbreviation GAx
gibberelin Ax 相似文献
39.
Glucoraphasatin is an atypical glucosinolate mainly found in Raphanus sativus roots and sprouts. This review focuses on the chemistry, the occurrence, and the biological properties of glucoraphasatin. 相似文献
40.