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Preliminary study of mechanism of action of SN38 derivatives. Physicochemical data,evidence of interaction and alkylation of DNA octamer d(GCGATCGC)2
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Beata Naumczuk Robert Kawęcki Wojciech Bocian Elżbieta Bednarek Jerzy Sitkowski Lech Kozerski 《Magnetic resonance in chemistry : MRC》2017,55(2):128-136
The synthesis of water‐soluble SN38 derivatives is presented, and their stability in solutions used during drug development studies has been investigated. A preliminary study of mechanism of action of 9‐aminomethyl SN38 is presented. Using NMR techniques, the interaction of the oligomer d(GCGATCGC)2 is studied, showing that the terminal GC base pairs are the main site of interaction. Using pulsed field gradient spin echo and mass spectroscopy, evidence of a spontaneous alkylation reaction of the DNA oligomer with SN38 derivatives is presented. A proposed mechanism of reaction is suggested. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
445.
Beata Randrianantoanina 《Israel Journal of Mathematics》1999,113(1):45-60
We show that the Rudin-Plotkin isometry extension theorem inL
pimplies that whenX andY are isometric subspaces ofL
pandp is not an even integer, 1≤p<∞, thenX is complemented inL
pif and only ifY is; moreover, the constants of complementation ofX andY are equal. We provide examples demonstrating that this fact fails whenp is an even integer larger than 2. 相似文献
446.
Lukasz Banach Lukasz Janczewski Jakub Kajdanek Katarzyna Milowska Joanna Kolodziejczyk-Czepas Grzegorz Galita Wioletta Rozpedek-Kaminska Ewa Kucharska Ireneusz Majsterek Beata Kolesinska 《Molecules (Basel, Switzerland)》2022,27(7)
Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage. 相似文献
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Beata A. Wolucka Edmond de Hoffmann 《Journal of the American Society for Mass Spectrometry》1995,6(6):516-520
Very low energy collision-induced dissociation of the deprotonated molecules of glycosyl esters of nucleoside pyrophosphates results in distinct fragmentation patterns that depend on the cis-trans configuration of the phosphodiester and 2″-hydroxyl groups of the glycosyl residue. In tandem mass spectrometry, sugar nucleotides with cis configuration produce only one, very abundant fragment that corresponds to nucleoside monophosphate, whereas nucleotides with trans configuration give weak signals for the nucleoside di- and monophosphates and their dehydration products. This empirical rule holds for sugar nucleotides that have a free 2″-hydroxyl group and no alternative charge location. Owing to its simplicity, sensitivity, and tolerance of impurities, fast-atom bombardment-tandem mass spectrometry represents a suitable method for determination of the anomeric linkage of glycosyl esters of nucleoside pyrophosphates if the absolute configuration of glycosyl residue is known and the compound fulfills the above-mentioned requirements. 相似文献
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Anita
liwiska Ramona Figat Anna Zgadzaj Beata Wileska Aleksandra Misicka Grzegorz Nacz-Jawecki Agnieszka Pietrosiuk Katarzyna Sykowska-Baranek 《Molecules (Basel, Switzerland)》2022,27(1)
Hairy root cultures are considered as a valuable source of bioactive phytoconstituents with expanding applicability for their production. In the present study, hairy root cultures of Polyscias filicifolia (Araliaceae), a traditional Southeast Asian medicinal plant, were established. The transformation with Agrobacterium rhizogenes ATCC 15834 allowed to obtain 15 root lines. The K-1 line, demonstrating the highest growth capabilities, was subjected to further investigations. To enhance the biosynthetic potential of hairy roots, methyl jasmonate elicitation approach was applied (MeJA; at different doses and exposure time), with subsequent transfer of elicited roots to control medium. This strategy resulted in chlorogenic acid production up to 1.59 mg/g dry weight. HPLC-PDA-ESI-MS analysis demonstrated variation in extracts composition and allowed to identify different caffeic and ferulic acid derivatives. Next, cytotoxic, antigenotoxic, and anti-photogenotoxic properties of hairy roots extracts were determined. None of the tested extracts were cytotoxic. In addition, they demonstrated significant antigenotoxic activity with the highest protective potential; up to 52% and 49% of inhibition of induction ratio (IR) induced by the 2-aminoanthracene was revealed for extracts derived from hairy roots elicited for 3 days with 50 µM MeJA and roots elicited for 7 days with 100 µM MeJA and then transferred for 30 days to control medium, respectively. These same extracts exhibited the highest anti-photogenotoxic potential, up to 36% of inhibition of chloropromazine-induced genotoxicity. 相似文献