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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
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Yukio Sasaki Misato Takimoto Kyoko Oda Thomas Früh Michihiro Takai Toshikazu Okada Seiji Hori 《Journal of neurochemistry》1997,68(5):2194-2200
Abstract: Excessive release of glutamate, from glial cells as well as neurons, is thought to be a major cause of neuronal death in ischemia. To investigate glutamate release from glial cells, we measured glutamate efflux from cultures of rat astrocytes preloaded with l -[3 H]-glutamate. Glutamate efflux was induced by either 60 m M KCl or Na+ -free medium, suggesting that the efflux is due to the reversed operation of a Na+ - and K+ -coupled glutamate uptake machinery. While investigating various neuropeptides and neurotransmitters, we found that endothelin (ET) specifically induced efflux of glutamate. Northern blot analysis and binding study showed that the ET type B receptor (ETB -R) subtype was expressed two to three times more densely than the ET type A receptor (ETA -R) in astrocytes. The ETB -R antagonist IRL 2500 partially inhibited efflux of glutamate induced by 1 n M ET-1 in a concentration-dependent manner, causing a maximal inhibition of 60% at 1 µ M . However, the ETA -R antagonist BQ-123 did not cause significant inhibition even at 10 µ M . Combination of both antagonists completely inhibited the ET-1-induced efflux. These results indicate that both receptor subtypes are involved in efflux of glutamate with a major contribution from the ETB -R. Our findings suggest that ET, which is known to be released in ischemia, may exacerbate neurodegeneration by stimulating efflux of glutamate. 相似文献
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Shin-ichiro Kurimoto Kyoko Suzuki Mamoru Okasaka Yoshiki Kashiwada Olimjon K. Kodzhimatov Yoshihisa Takaishi 《Phytochemistry letters》2012,5(4):729-733
Five new eudesmane- (1–5), two new guaiane- (6 and 7) and one new germacrane-type (8) sesquiterpene lactone glucosides were isolated from the H2O-soluble fraction of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configuration of 1 was determined by modified Mosher's method. 相似文献
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The production of the leukemic cell-growth-promoting factor (LGF) in TGF-β1-treated fibroblast cells was studied. BALB/c3T3 mouse fibroblast(3T3) cells cultured in Eagle's medium containing a low concentration of TGF-β1 (0.04-1 ng/ml) secreted 3-5 times more LGF than the cells cultured in the absence of TGF-β1. The amount of LGF secretion was dose-dependent on the concentration of post-cultured medium and time-dependent after the addition of TGF-β1. Similar findings were obtained in human diploid fibroblasts, WI-38 cells. LGF is a 18KD glycoprotein that is acid-stable but heat-unstable. 相似文献
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Toshio Yoshida Akira Komatsu Motoichi Indo 《Bioscience, biotechnology, and biochemistry》2013,77(9):824-831
The isomerization and racemization of menthol isomers have been investigated with copper chromite and Raney nickel catalyst or sodium mentholates. The equilibrium concentration has been found to correspond to 55~56% of menthol with the catalytic isomerization, whereas to 74~75% of menthol with sodium mentholates. From these data, the free energy difference between equatorial and axial group in menthols is calculated to be about 0.5~0.6 Kcal./mole for hydroxyl and 1.4~1.5 Kcal./mole for methyl at 200°C. 相似文献
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