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排序方式: 共有206条查询结果,搜索用时 484 毫秒
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Galina F. Makhaeva Nadezhda V. Kovaleva Natalia P. Boltneva Elena V. Rudakova Sofya V. Lushchekina Tatiana Yu. Astakhova Igor V. Serkov Alexey N. Proshin Eugene V. Radchenko Vladimir A. Palyulin Jan Korabecny Ondrej Soukup Sergey O. Bachurin Rudy J. Richardson 《Molecules (Basel, Switzerland)》2022,27(3)
Using two ways of functionalizing amiridine—acylation with chloroacetic acid chloride and reaction with thiophosgene—we have synthesized new homobivalent bis-amiridines joined by two different spacers—bis-N-acyl-alkylene (3) and bis-N-thiourea-alkylene (5) —as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). All compounds exhibited high inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity for BChE. These new agents displayed negligible carboxylesterase inhibition, suggesting a probable lack of untoward drug–drug interactions arising from hydrolytic biotransformation. Compounds 3 with bis-N-acyl-alkylene spacers were more potent inhibitors of both cholinesterases compared to compounds 5 and the parent amiridine. The lead compounds 3a–c exhibited an IC50(AChE) = 2.9–1.4 µM, IC50(BChE) = 0.13–0.067 µM, and 14–18% propidium displacement at 20 μM. Kinetic studies of compounds 3a and 5d indicated mixed-type reversible inhibition. Molecular docking revealed favorable poses in both catalytic and peripheral AChE sites. Propidium displacement from the peripheral site by the hybrids suggests their potential to hinder AChE-assisted Aβ42 aggregation. Conjugates 3 had no effect on Aβ42 self-aggregation, whereas compounds 5c–e (m = 4, 5, 6) showed mild (13–17%) inhibition. The greatest difference between conjugates 3 and 5 was their antioxidant activity. Bis-amiridines 3 with N-acylalkylene spacers were nearly inactive in ABTS and FRAP tests, whereas compounds 5 with thiourea in the spacers demonstrated high antioxidant activity, especially in the ABTS test (TEAC = 1.2–2.1), in agreement with their significantly lower HOMO-LUMO gap values. Calculated ADMET parameters for all conjugates predicted favorable blood–brain barrier permeability and intestinal absorption, as well as a low propensity for cardiac toxicity. Thus, it was possible to obtain amiridine derivatives whose potencies against AChE and BChE equaled (5) or exceeded (3) that of the parent compound, amiridine. Overall, based on their expanded and balanced pharmacological profiles, conjugates 5c–e appear promising for future optimization and development as multitarget anti-AD agents. 相似文献
173.
Back Cover: Ternary Hybrid γ‐Fe2O3/CrVI/Amine Oxidase Nanostructure for Electrochemical Sensing: Application for Polyamine Detection in Tumor Tissue (Chem. Eur. J. 20/2016)
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Dr. Emanuela Bonaiuto Dr. Massimiliano Magro Dr. Davide Baratella Dr. Petr Jakubec Elisabetta Sconcerle Dr. Milo Terzo Dr. Giovanni Miotto Dr. Alberto Macone Prof. Enzo Agostinelli Dr. Silvano Fasolato Dr. Rina Venerando Prof. Gabriella Salviulo Dr. Ondrej Malina Prof. Radek Zboril Prof. Dr. Fabio Vianello 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(20):6988-6988
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Darina Lankova Andrea SvarcovaKamila Kalachova Ondrej LacinaJana Pulkrabova Jana Hajslova 《Analytica chimica acta》2015
In the present study, a novel analytical approach for the simultaneous determination of 27 brominated flame retardants (BFRs), namely polybrominated diphenyl ethers (PBDEs), isomers of hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA) and several novel BFRs (NBFRs), together with 18 perfluoroalkyl substances (PFASs) in indoor dust was developed and validated. To achieve integrated isolation of analytes from the sample and their fractionation, a miniaturized method based on matrix solid phase dispersion (MSPD) was employed. Principally, after mixing the dust (<0.1 g) with the Florisil®, the mixture was applied on the top of a sorbent (Florisil®) placed in glass column and then analytes were eluted using solvents with different polarities. For the identification/quantification of target compounds largely differing in polarity, complementary techniques represented by gas and liquid chromatography coupled to tandem mass spectrometry (GC–MS/MS and LC–MS/MS) were used. The results of validation experiments, which were performed on the SRM 2585 material (for PBDEs, HBCDs and TBBPA), were in accordance with the certified/reference values. For other analytes (NBFRs and PFASs), the analysis of an artificially contaminated blank dust sample was realized. The method recoveries for all target compounds ranged from 81 to 122% with relative standard deviations lower than 21%. The quantification limits were in the range of 1–25 ng g−1 for BFRs and 0.25–1 ng g−1 for PFASs. Finally, 18 samples (6 households × 3 sampling sites) were analyzed. The high variability between concentrations of PFASs and BFRs in the dust samples from various households as well as collecting sites in a respective house was observed. The total amounts of PFASs and BFRs were in the range of 1.58–236 ng g−1 (median 10.6 ng g−1) and 39.2–2320 ng g−1 (median 325 ng g−1), respectively. It was clearly shown that dust from the indoor environment might be a significant source of human exposure to various organohalogen pollutants. 相似文献
178.
Preconcentration based on paramagnetic microparticles for the separation of sarcosine using hydrophilic interaction liquid chromatography coupled with coulometric detection
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Ondrej Zitka Zbynek Heger Marketa Kominkova Sylvie Skalickova Sona Krizkova Vojtech Adam Rene Kizek 《Journal of separation science》2014,37(5):465-575
Sarcosine has been identified as a potential prostate cancer marker. To provide determination of this compound, a number of methods are developing. In this study, we optimized a method for its separation by hydrophilic interaction LC with electrochemical detection (ED). Due to the fact that mobile phases commonly used for this type of separation altered the LODs measured by electrochemical detectors, we applied postcolumn dosing of buffer suitable for ED. The optimized conditions were mobile phase A acetonitrile, mobile phase B water in the ratio A/B 70:30, with postcolumn addition of mobile phase C (200 mM phosphate buffer pH 9). The optimal mixing ratio was A + B/C 1:1 with a flow rate of 0.80 mL/min (0.40 + 0.40 mL/min) and detection potential of 1000 mV. Due to the optimization of the parameters for effective separation, which had to meet the optimal parameters of ED, we reached a good resolution for separation also with a good LOD (100 nM). In addition, we successfully carried out sarcosine analysis bound on our modified paramagnetic microparticles with the ability to preconcentrate sarcosine isolated from artificial urine. 相似文献
179.
Natalia Cernei Zbynek Heger Pavel Kopel Jiri Skladanka Ondrej Zitka Vojtech Adam Rene Kizek 《Chromatographia》2014,77(21-22):1451-1459
This study aims at the possibility of single structured paramagnetic microparticles (PMPs), composed of maghemite (γ-Fe2O3) core modified with chitosan called MAN8, or tetraethyl orthosilicate covered with Dowex called MAN35, to be helpful for isolation of biogenic amines prior to their further analysis. Primarily, we synthesized and characterized PMPs. To obtain the information about bead morphology, scanning electron microscopy was employed. Furthermore, X-ray fluorescence was employed to carry out the elemental composition analyses. To obtain further insight into interaction between PMP surface and biogenic amines, scanning electron microscope was employed. It was shown that binding of biogenic amines causes increase of relative current response of deprotonated microparticles. We tested the specificity of PMPs to bind biogenic amines on histamine, tyramine, spermine, spermidine, putrescine, and cadaverine. We found that two types of our PMPs were able to selectively bind spermidine, cadaverine, and histamine in the case of MAN35; and histamine, tyramine, and putrescine in the case of MAN8. Finally, we carried out the analyses of real samples obtained from patients suffering from prostate carcinoma, where histamine was determined as the most abundant biogenic amine (10.456–13.654 µg mL?1). The prepared PMPs were able to isolate the biogenic amines from real samples, and thus they may be helpful in construction of biosensors, or Lab-on-a-Chip platforms, enabling less painful, and more rapid diagnosis of prostate cancer. 相似文献
180.
Neglect of end effects in Couette rotational viscometry introduces a 10–30% error in the estimate of shear stress at the spindle
surface. Actual deviations depend on the shear-thinning level of a given sample. We tackle the end effect for the standard
sensor Z40 DIN according to the ISO 3219 by solving the related 2D boundary-value problem for a class of shear-thinning viscosity
functions. The pseudosimilarity method of treating the primary data leaves an error of about 0.5% in shear stresses. Further
reduction in the errors needs a full numerical simulation for each point of the primary data based on a suitable wide-range
representation of the viscosity function. To support a high accuracy of torque calibrations, the effect of inertia on torque
for Newtonian liquids in standard sensor Z40 DIN at Re < 500 is calculated using the FLUENT 6.2 commercial software.
Paper was presented at the 3rd Annual Rheology Conference, AERC 2006, April 27–29, 2006, Crete, Greece. 相似文献