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71.
72.
Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti‐Alzheimer Disease Drug NQ‐Trp
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Dr. Olivia Berthoumieu Dr. Phuong H. Nguyen Maria P. del Castillo‐Frias Sabrina Ferre Dr. Bogdan Tarus Dr. Jessica Nasica‐Labouze Dr. Sabrina Noël Dr. Olivier Saurel Dr. Claire Rampon Prof. Dr. Andrew J. Doig Prof. Dr. Philippe Derreumaux Prof. Dr. Peter Faller 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(36):12657-12666
Inhibition of the aggregation of the monomeric peptide β‐amyloid (Aβ) into oligomers is a widely studied therapeutic approach in Alzheimer’s disease (AD). Many small molecules have been reported to work in this way, including 1,4‐naphthoquinon‐2‐yl‐L ‐tryptophan (NQ‐Trp). NQ‐Trp has been reported to inhibit aggregation, to rescue cells from Aβ toxicity, and showed complete phenotypic recovery in an in vivo AD model. In this work we investigated its molecular mechanism by using a combined approach of experimental and theoretical studies, and obtained converging results. NQ‐Trp is a relatively weak inhibitor and the fluorescence data obtained by employing the fluorophore widely used to monitor aggregation into fibrils can be misinterpreted due to the inner filter effect. Simulations and NMR experiments showed that NQ‐Trp has no specific “binding site“‐type interaction with mono‐ and dimeric Aβ, which could explain its low inhibitory efficiency. This suggests that the reported anti‐AD activity of NQ‐Trp‐type molecules in in vivo models has to involve another mechanism. This study has revealed the potential pitfalls in the development of aggregation inhibitors for amyloidogenic peptides, which are of general interest for all the molecules studied in the context of inhibiting the formation of toxic aggregates. 相似文献
73.
AM Cardoso SM Alexandre CM Barros AJ Correia NM Nibbering 《Rapid communications in mass spectrometry : RCM》1999,13(19):1885-1888
The collision-induced dissociation (CID) of deprotonated arylalkylamines of general formula R(1)C(6)H(4)CHR(2)CH(2)NR(3)(2) (where R(1) = H, OH, F or NO(2); R(2) = H or OH; R(3) = H or CH(3)) generated by negative chemical ionization with H(2)O and D(2)O as ionizing reagents, is discussed. The negative chemical ionization mass spectra show that, in the absence of a hydroxy group in the aromatic ring, deprotonation takes place at the benzylic position whereas the proton is lost from the OH group when present. The nitro compound forms only M(-.) ions. The CID spectra of the deprotonated molecules show that fragmentations are strongly dependent on the structural features of the molecules, namely the presence or absence of substituents in the aromatic ring or aliphatic chain. Copyright 1999 John Wiley & Sons, Ltd. 相似文献
74.
AM Johnston CM Scrimgeour MO Henry LL Handley 《Rapid communications in mass spectrometry : RCM》1999,13(14):1531-1534
The conversion of nitrate (NO(3)(-)) to 1-phenylazo-2-naphthol (Sudan-1) has been examined as a method for natural abundance measurement of delta(15)N of NO(3)(-). The reaction results in dilution of NO(3)(-)-N with only one reagent-derived N and the product is readily concentrated from dilute samples by reverse phase chromatography. There is systematic isotopic fractionation during the reaction, but this can be allowed for by analysing known NO(3)(-) standards along with each sample set. Sudan-1 prepared from surface water samples containing approximately 50 &mgr;g NO(3)(-)-N can be analysed by automated continuous flow isotope ratio mass spectrometry with a precision of 0.2 per thousand (one standard deviation) and the accuracy is not affected by interference from other nitrogenous species in the sample or reagents. Copyright 1999 John Wiley & Sons, Ltd. 相似文献
75.
Xue-Xin Li Tuo Ji Jun-Yang Gao Wei-Chao Chen Ye Yuan Hao-Yan Sha Roland Faller Guo-Gang Shan Kui-Zhan Shao Xin-Long Wang Zhong-Min Su 《Chemical science》2022,13(16):4573
Fully reduced polyoxometalates are predicted to give rise to a broad and strong absorption spectrum, suitable energy levels, and unparalleled electronic and optical properties. However, they are not available to date. Here, an unprecedented fully reduced polyoxomolybdate cluster, namely Na8[MoV60O140(OH)28]·19H2O {MoV60}, was successfully designed and obtained under hydrothermal conditions, which is rare and is the largest fully reduced polyoxometalate reported so far. The MoV60 molecule describes one Keggin {ε-Mo12} encapsulated in an unprecedented {Mo24} cage, giving rise to a double truncated tetrahedron quasi-nesting architecture, which is further face-capped by another four {Mo6} tripods. Its crystalline stability in air, solvent tolerance, and photosensitivity were all shown. As a cheap and robust molecular light-absorber model possessing wide light absorption, MoV60 was applied to build a co-sensitized solar cell photoelectronic device along with N719 dyes and the optimal power conversion efficiency was 28% higher than that of single-dye sensitization. These results show that MoV60 polyoxometalate could serve as an ideal model for the design and synthesis of all-inorganic molecular light-absorbers for other light-driven processes in the future.An unprecedented fully reduced {MoV60} POM served as a cheap and robust molecular light-absorber model possessing wide light absorption and was applied to build a co-sensitized solar cell photoelectronic device. 相似文献
76.
Hanane Benzeid Emmanuelle Mothes El Mokhtar Essassi Peter Faller Geneviève Pratviel 《Comptes Rendus Chimie》2012,15(1):79-85
Simple and easy to prepare quinoxaline derivatives proved able to stain amyloid fibers such as aggregated lysozyme and Aβ(1-40)-peptide by a fluorescence “turn on” mechanism. Thienoquinoxaline 1 allowed the detection of lysozyme and Aβ(1-40) fibers at λ = 555 and 532 nm, respectively, with excitation at λ = 450 nm. Styryl-quinoxaline 2 stained lysozyme and Aβ(1-40) fibers with fluorescence at λ = 579 and 567 nm, respectively, upon excitation at λ = 453 nm. The apparent Kd values for Aβ(1-40) fibers were 77 and 294 nM for 1 and 2, respectively. The sensitivity of the aggregates detection assay with these new dyes was higher than that of thioflavin T. Considering their unique fluorescence properties compared to other dyes reported in the field, they can be considered as additional staining tools for the detection and studies of peptide/protein aggregation. 相似文献
77.
Sasaki I Bijani C Ladeira S Bourdon V Faller P Hureau C 《Dalton transactions (Cambridge, England : 2003)》2012,41(21):6404-6407
Coordination of a cyclometallated Pt(II) complex (1) to an amyloid-β peptide was probed by NMR and ESI-MS. Furthermore, EPR showed that binding of 1 to the Cu(II)-amyloid-β species resulted in a reshuffling of the Cu(II) coordination sphere, which was absent or lower for the sister non cyclometallated Pt(II) complexes. 相似文献
78.
Inhibition of Cu-amyloid-β by using bifunctional peptides with β-sheet breaker and chelator moieties
Jensen M Canning A Chiha S Bouquerel P Pedersen JT Østergaard J Cuvillier O Sasaki I Hureau C Faller P 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(16):4836-4839
Breaking the mold: Inhibition of toxic amyloid-β (Aβ) aggregates and disruption of Cu-Aβ with subsequent redox-silencing of Cu have been considered promising strategies against Alzheimer's disease. The design and proof of concept of simple peptides containing a Cu-chelating/redox-silencing unit and an Aβ-aggregation inhibition unit (β-sheet breaker) is described (see scheme). 相似文献
79.
We present a simulation study focusing on modulations of the stress, or lateral pressure, profiles of lipid bilayer phases by addition of a sterol, ergosterol, at multiple temperatures. A major redistribution of lateral and normal pressures across the gel-phase bilayer required 10 mol % sterol in comparison to a gradual redistribution beginning at 20 mol % for the liquid phase. Stress profiles across all temperatures converged at 30 mol % ergosterol. Redistribution and merging of stress profiles, associated with structural alterations, are coincident with experimentally observed modulations in mechanical properties and therefore are suggested as the mechanism of action for this biologically necessary role of sterols. 相似文献
80.
C. Faller G. Henze N. Stojko S. Saraeva K. Brainina 《Fresenius' Journal of Analytical Chemistry》1997,358(6):670-676
The paper describes the determination of tin by ASV using modified thick film electrodes. Three different types of electrodes
were developed: One modified with a mixture of Nafion and mercury(II)acetate, one modified with diethyldithiocarbamate (DDC)
or pyrrolidinedithiocarbamate (PDC) and mercury(II)acetate, and one modified with calomel. The analyte was accumulated on
the electrode surface after special electrochemical pretreatment of the modified electrode. After recording the voltammogram
the electrodes were electrochemically regenerated. By virtue of their lifetime and their measurement reproducibility, we preferred
the DDC and PDC modified electrodes. They can be used for months without changing their chemical characteristics. The linear
range for tin determination with these electrodes is between 1 and 100 μg/L; the detection limit was calculated as 0.9 μg/L.
The electrodes were applied to the direct determination of tin in different canned fruit juices without special sample pretreatment.
Received: 20 December 1996 / Revised: 11 March 1997 / Accepted: 13 March 1997 相似文献