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31.
Luis Santos-Molina Alexa Herrerias Charles N. Zawatsky Ozge Gunduz-Cinar Resat Cinar Malliga R. Iyer Casey M. Wood Yuhong Lin Bin Gao George Kunos Grzegorz Godlewski 《Molecules (Basel, Switzerland)》2021,26(16)
Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a “two-bottle” as well as a “drinking in the dark” paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia. 相似文献
32.
Charlene M. Czerniak William B. Weber Alexa Sandmann John Ahern 《School science and mathematics》1999,99(8):421-430
Integrated curricula has gained a great deal of acceptance among educators. Many educators provide testimonials about the effectiveness of units they teach, and many professional organizations stress integration across the curriculum. However, few empirical studies exist to support the notion that an integrated curriculum is any better than a well-designed traditional curriculum. Some educators question integration across the curriculum, because in the effort to integrate topics, science and mathematics content becomes superficial and trivial. This paper presents a review of the literature on integrated curricula. It concludes with a call to action for members of School Science and Mathematics Association. 相似文献
33.
Alpha recoil sources of221Rn were used to study the level structure of217Po and the ground state of213Pb. The half-life of217Po was measured to be (1.6±0.2) s. When combined with unpublished data, an alpha-decay hindrance factor (HF) of 1.3 was obtained
for the alpha-decay, strongly suggesting a g9/2 → g9/2 transition between217Po and213Pb ground states. Alpha-gamma coincidence studies confirm the previously observed 11/2+ band head in217Po. It is suggested that an unobserved 9/2+ ground state lies below the 11/2+ state in217Po and an attempt is made to observe connecting links between these two parts of the217Po level scheme. 相似文献
34.
Manesiotis P Hall AJ Emgenbroich M Quaglia M De Lorenzi E Sellergren B 《Chemical communications (Cambridge, England)》2004,(20):2278-2279
Using 1-(4-styryl)-3-(3-nitrophenyl)urea as host monomer for the imprinting of Z-(D or L)-Glu, a polymeric receptor exhibiting strong enantioselectivity and a change in color intensity upon binding of the guest was obtained. 相似文献
35.
De Lorenzi E Grossi S Massolini G Giorgetti S Mangione P Andreola A Chiti F Bellotti V Caccialanza G 《Electrophoresis》2002,23(6):918-925
Dialysis-related amyloidosis is a disease in which partial unfolding of beta(2)-microglobulin plays a key pathogenetic role in the formation of the amyloid fibrils. We have recently demonstrated that a partially unfolded conformer of beta(2)-microglobulin is involved in fibrillogenesis and that this species is significantly populated under physiological conditions. In this work capillary electrophoresis has been used to measure the equilibrium between the native protein and this conformer in samples known to have a higher or lower amyloidogenic potential, namely full-length beta(2)-microglobulin, two truncated species and a mutant, created by replacing histidine in position 31 with thyrosine. In addition, for all protein species folding stability experiments have been carried out by monitoring the secondary structure by circular dichroism at increasing concentrations of guanidinium chloride. The values of free energy of unfolding in the absence of denaturant, obtained by elaboration of these experiments, were found to be inversely correlated to the area percent of the partially unfolded conformer, as measured by capillary electrophoresis. Affinity capillary electrophoresis experiments have been also carried out under nondenaturing conditions to assess the affinity of copper and suramin to either the native form or the conformational intermediate of full-length beta(2)-microglobulin. 相似文献
36.
Factor X is a blood clotting protein that associates at membrane surfaces to become activated during the coagulation cascade. A molecular level understanding of the protein-membrane phospholipid interactions has not been reached, although it is thought that the protein binds to phospholipids in the presence of calcium through a bridge with the Gla (gamma-carboxyglutamic acid) domain on the protein. In this work, phospholipid Langmuir monolayers have been utilized as model membranes to study factor X association with phospholipid membrane components. Surface pressure measurements indicate that subphase addition of sodium, magnesium, and calcium ions enhances protein penetration of the lipid monolayer, with the largest association found with calcium ions in the subphase. Fluorescence microscopy images collected after protein penetration of lipid monolayers indicate monolayer condensation in the presence of sodium and magnesium ions. Aggregation of lipid domains is induced when calcium is in the subphase, indicating binding-induced flocculation of surface lipid aggregates. Calcium binding to factor X likely causes a conformational change which allows protein-membrane interaction via hydrophobic association with lipid molecules. 相似文献
37.
Carazzone C Colombo R Quaglia M Mangione P Raimondi S Giorgetti S Caccialanza G Bellotti V De Lorenzi E 《Electrophoresis》2008,29(7):1502-1510
Human beta2-microglobulin (beta2-m) is a small amyloidogenic protein responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, to possibly inhibit protein misfolding and amyloid fibril formation. The search of a strong ligand of this protein is extremely challenging: by using CE in affinity and refolding experiments we study the effect that previously selected sulfonated molecules have on the equilibrium between the native form and an ensemble of conformers populating the slow phase of beta2-m folding. These data are correlated with the effect that the same molecules exert on in vitro fibrillogenesis experiments. 相似文献
38.
Voltammetry of immobilized microparticles was used to find arsenic and heavy metals in contaminated soils from areas with long history of industrial development. Traditional sample dissolution and extraction procedures are time consuming and might distort the chemical equilibrium of the sample causing a change in the original physicochemical forms of distribution. A minute amount of sample was physically attached to the carbon paste working electrode surface and an anodic differential pulse voltammogram was obtained without disturbing the original equilibria. The position of the peaks revealed the presence of Pb and Cu and As(V) and As(III) for the most contaminated soils. As(III) was detected when its percentage in soil was more than 0.001% (expressed as As2O3). The limit of detectability was strongly dependent on the presence of iron(III) which increased the signal 10 times. 相似文献
39.
Laura Bertoletti Julie Schappler Raffaella Colombo Serge Rudaz Rob Haselberg Elena Domínguez-Vega Sara Raimondi Govert W. Somsen Ersilia De Lorenzi 《Analytica chimica acta》2016
In this work we explored the feasibility of different CE-ESI-MS set-ups for the analysis of conformational states of an intact protein. By using the same background electrolyte at quasi physiological conditions (50 mM ammonium bicarbonate, pH 7.4) a sequential optimization was carried out, initially by evaluating a sheath-liquid interface with both a single quadrupole (SQ) and a time-of-flight (TOF) mass spectrometer; then a sheathless interface coupled with high-resolution QTOF MS was considered. Beta2-microglobulin has been taken as a model, as it is an amyloidogenic protein and its conformational changes are strictly connected to the onset of a disease. The separation of two conformers at dynamic equilibrium is achieved all the way down to the MS detection. Notably, the equilibrium ratio of the protein conformers is maintained in the electrospray source after CE separation. Strengths and weaknesses of each optimized set-up are emphasized and their feasibility in unfolding studies is evaluated. In particular, ESI-TOF MS can assign protein forms that differ by 1 Da only and sheathless interfacing is best suited to preserve protein structure integrity. This demonstrates the CE-ESI-MS performance in terms of separation, detection and characterization of conformational species that co-populate a protein solution. 相似文献
40.