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81.
When 3-C-sulfonyl-pent-2-enofuranosides and 3-C-sulfonyl-hex-2-enofuranosides were reacted with primary and secondary amines, only the beta-anomeric methoxy group of the pent-2-enofuranoside did not cause any hindrance to incoming nitrogen nucleophiles. This resulted in the 'unusual' addition of amines, in which the diastereoselectivity of the reaction was overwhelmingly in favor of amino sugars of the D-arabino configuration. Selected products were desulfonylated to obtain a new class of beta-anomeric 2-amino-2,3-dideoxy-D-threo-pentofuranosides. 相似文献
82.
Purpose Fenretinide, 4-(N-hydroxyphenyl) retinamide, (4-HPR) is a well tolerated analog of alltrans retinoic acid. The gangliosideGM3, is a non-specific
inhibitor of EGF receptor autophosphorylation (EGFR-phos). Both compounds were found preferentially cytotoxic to malignant
and proliferating cells when compared to non-proliferating normal brain cells. Some of the small molecule inhibitors of EGFR-phos
are also known to inhibit growth of brain tumors at relatively non-toxic doses. The purpose of this investigation was to evaluate
if 4-HPR and inhibitors of EGFR-phos could be used together in the treatment of brain tumors. Methods The 9L rat gliosarcoma cells were treated in vitro with 4-HPR either alone or in combination with the non-specific or specific
inhibitors of EGFR-phos, GM3 or AG-1478, respectively. The relative viability of the control and treated cells was determined
using 3-(4,5-imethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The experimental data were analyzed for statistical
significance. Results In contrast to the expected additive/synergistic effect on cell growth inhibition, the sub-toxic and toxic concentrations
of 4-HPR protected GM3 treated cells. The viable cells were 3.86 times higher following GM3 plus 4-HPR treatments compared
to GM3 treatment alone. Additionally, a specific inhibitor of EGFR-phos signaling, AG-1478 caused a concentration dependent
protection of cells from the toxicity of 4-HPR. Our results show counteracting cytotoxic responses of 4-HPR and EGFR-phos
inhibitors when used together in 9L rat gliosarcoma cells. 相似文献
83.
Dwivedi AP Kumar S Varshney V Singh AB Srivastava AK Sahu DP 《Bioorganic & medicinal chemistry letters》2008,18(7):2301-2305
A series of novel N-acyl-2-arylethylamines and N-acyl-3-coumarylamines were synthesized and evaluated for their antihyperglycemic activity. Compounds 3g and 6d exhibited lowering of postprandial plasma glucose by 30.7%, 23.3% in SLM and 25.6%, 25.4% in STZ models respectively which is significant compared to metformin and glybenclamide. Other compounds exhibited moderate to good activity ranging from 19.5% to 32.8% in SLM and 3.26% to 25.4% in STZ models. 相似文献
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Omar M. Khdour Indrajit Bandyopadhyay Sandipan Roy Chowdhury Nishant P. Visavadiya Sidney M. Hecht 《Bioorganic & medicinal chemistry》2018,26(12):3359-3369
Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder resulting from reduced expression of the protein frataxin (FXN). Although its function is not fully understood, frataxin appears to help assemble iron sulfur clusters; these are critical for the function of many proteins, including those needed for mitochondrial energy production. Finding ways to increase FXN levels has been a major therapeutic strategy for this disease. Previously, we described a novel series of methylene violet analogues and their structural optimization as potential therapeutic agents for neurodegenerative and mitochondrial disorders. Presently, a series of methylene blue analogues has been synthesized and characterized for their in vitro biochemical and biological properties in cultured Friedreich’s ataxia lymphocytes. Favorable methylene blue analogues were shown to increase frataxin levels and mitochondrial biogenesis, and to improve aconitase activity. The analogues were found to be good ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I and from glutathione depletion. The analogues also preserved mitochondrial membrane potential and augmented ATP production. Our results suggest that analogue 5, emerging from the initial structure of the parent compound methylene blue (MB), represents a promising lead structure and lacks the cytotoxicity associated with the parent compound MB. 相似文献
90.
Abdel Rahman Abdel Fattah Sarah Mishriki Tobias Kammann Rakesh P. Sahu Fei Geng Ishwar K. Puri 《Biometals》2018,31(4):605-616
Contrasting agents (CAs) that are administered to patients during magnetic resonance imaging to facilitate tumor identification are generally considered harmless. However, gadolinium (Gd) based contrast agents can be retained in the body, inflicting specific cell line cytotoxicity. We investigate the effect of Gadopentatic acid (Gd-DTPA) on human breast adenocarcinoma MCF-7 cells. These cells exhibit a toggle switch response: exposure to 0.1 and 1 mM concentrations of Gd-DTPA enhances proliferation, which is hindered at a higher 10 mM concentration. Proliferation is enhanced when cells transition to 3D morphologies in post confluent conditions. The proliferation dependence on the concentration of CA is absent for Hs 578T and MDA-MB-231 triple negative cell lines. MCF-7 cells reveal a double toggle switch related to the expression of VEGF, which goes through high–low–high downregulation when cells are exposed to 0.1, 1, and 10 mM Gd-DTPA, respectively. Finally, doxorubicin drug response is assessed, which also reveals a double toggle switch behavior, where drug cytotoxicity exhibits a nonlinear dependence on the CA concentration. A toggle switch in cell characteristics that are exposed to 1 mM of Gd-DTPA amplifies the importance of this threshold, affecting several cell behaviors if surpassed. This work emphasizes the important effects that CAs can have on cells, specifically Gd-DTPA on MCF-7 cells, and the implications for cell growth and drug response during clinical and synthetic biology procedures. 相似文献