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141.
Diaz-Montero CM Wang Y Shao L Feng W Zidan AA Pazoles CJ Montero AJ Zhou D 《Free radical biology & medicine》2012,52(9):1560-1568
The oxidized glutathione mimetic NOV-002 is a unique anti-tumor agent that not only has the ability to inhibit tumor cell proliferation, survival, and invasion, but in some settings can also ameliorate cytotoxic chemotherapy-induced hematopoietic and immune suppression. However, the mechanisms by which NOV-002 protects the hematopoietic and immune systems against the cytotoxic effects of chemotherapy are not known. Therefore, in this study we investigated the mechanisms of action of NOV-002 using a mouse model in which hematopoietic and immune suppression was induced by cyclophosphamide (CTX) treatment. We found that NOV-002 treatment in a clinically comparable dose regimen attenuated CTX-induced reduction in bone marrow hematopoietic stem and progenitor cells (HSPCs) and reversed the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), which led to a significant improvement in hematopoietic and immune functions. These effects of NOV-002 may be attributable to its ability to modulate cellular redox. This suggestion is supported by the finding that NOV-002 treatment upregulated the expression of superoxide dismutase 3 and glutathione peroxidase 2 in HSPCs, inhibited CTX-induced increases in reactive oxygen species production in HSPCs and MDSCs, and attenuated CTX-induced reduction of the ratio of reduced glutathione to oxidized glutathione in splenocytes. These findings provide a better understanding of the mechanisms whereby NOV-002 modulates chemotherapy-induced myelosuppression and immune dysfunction and a stronger rationale for clinical utilization of NOV-002 to reduce chemotherapy-induced hematopoietic and immune suppression. 相似文献
142.
Vu Thuy Khanh LeTrilling Sofia Banchenko Darius Paydar Pia Madeleine Leipe Lukas Binting Simon Lauer Andrea Graziadei Robin Klingen Christine Gotthold Jrg Bürger Thilo Bracht Barbara Sitek Robert Jan Lebbink Anna Malyshkina Thorsten Mielke Juri Rappsilber Christian MT Spahn Sebastian Voigt Mirko Trilling David Schwefel 《The EMBO journal》2023,42(5)
143.
Using the rat phrenic nerve diaphragm, cyproheptadine at concentrations of 1 to 8 mug/ml did not affect or slightly augmented indirect muscle twitches, but potentiated blockade by tubocurarine, decamethonium and succinylcholine, and antagonized the augmentation of twitches by neostigmine. Ketamine, choline and tetraethylammonium at concentrations causing no blockade produced, when given after cyproheptadine (6 mug/ml), a high degree of blockade. At concentrations of 9 to 20 mug/ml, cyproheptadine induced neuromuscular blockade which was slow in onset, more apparent at higher rate of stimulation and was not reversed by neostigmine, choline or tetraethylammonium. In the cat tibialis anterior muscle, it potentiated blockade by tubocurarine, decamethonium and succinylcholine, and blocked acetylcholine twitches. In the chick biventer cervicis muscle, the durg was more effective in blocking indirect twitches than responses to carbachol. 相似文献
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The results obtained indicate that the Chrysoperia carnea collected from Giza region (where no insecticidal treatments were used), were more sensitive to malathion than those of Kafr El-Sheikh, where insecticides were used intensively. In predator colonies which were treated repeatedly with malathion, the sensitivity to malathion decreased from the first to the fifth generation. On the other hand, insects of the reference colony, showed a considerable increase in sensitivity within the same generations. 相似文献
147.
Zainab M. Elsayed Wagdy M. Eldehna Marwa M. Abdel-Aziz Mahmoud A. El Hassab Eslam B. Elkaeed Tarfah Al-Warhi Hatem A. Abdel-Aziz Sahar M. Abou-Seri Eman R. Mohammed 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):384
Joining the global fight against Tuberculosis, the world''s most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site. 相似文献
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Metabolism of radioactive 17alpha-ethynylestradiol by women 总被引:1,自引:0,他引:1
Data on the urinary excretion and subsequent fractionation of radioactivity derived from 6,7-tritiated-17alpha-ethinyl estradiol (tritiated EE) are presented. Tritiated EE was administered orally to 9 women. 17alpha-ethinyl estradiol 2-methoxy-17alpha-ethinyl estradiol, 2 -hydroxy-17alpha-ethinyl estradiol 3-methyl ether, and D-homoestradiol-1 7abeta were identified as urinary metabolites by reverse isotope dilution. The extent of D-homoannulation was much less than that reported previously with rabbits. 相似文献