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151.
Let T denote a random duration until some event of interest. In the Cox model , if the value of Z at event time is unobserved, Dupuy and Mesbah (Lifetime Data Analysis 8 (2002) 99–115) have proposed to estimate the parameters β and by maximizing a likelihood obtained from a joint model for survival and the longitudinal covariate data. We show that the estimators derived from this joint likelihood are asymptotically normally distributed. To cite this article: J.-F. Dupuy et al., C. R. Acad. Sci. Paris, Ser. I 336 (2003). 相似文献
152.
Durka M Tikad A Périon R Bosco M Andaloussi M Floquet S Malacain E Moreau F Oxoby M Gerusz V Vincent SP 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(40):11305-11313
L-Heptoses (L-glycero-D-manno-heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D-glycero-D-manno-heptopyranose 7-phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1-, 2-, 6- and 7-positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6- and 7- positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D-glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC(50)=34 μM) and HldE (IC(50)=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence. 相似文献
153.
Nordqvist A Björkelid C Andaloussi M Jansson AM Mowbray SL Karlén A Larhed M 《The Journal of organic chemistry》2011,76(21):8986-8998
Cinnamaldehyde derivatives were synthesized in good to excellent yields in one step by a mild and selective, base-free palladium(II)-catalyzed oxidative Heck reaction starting from acrolein and various arylboronic acids. Prepared α,β-unsaturated aldehydes were used for synthesis of novel α-aryl substituted fosmidomycin analogues, which were evaluated for their inhibition of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase. IC(50) values between 0.8 and 27.3 μM were measured. The best compound showed activity comparable to that of the most potent previously reported α-aryl substituted fosmidomycin-class inhibitor. 相似文献
154.
In this paper, we present some new smoothing techniques to solve general nonlinear complementarity problems. Under a weaker condition than monotonicity as on the original problems, we prove convergence of our methods. We also present an error estimate under a general monotonicity condition. Some numerical tests confirm the efficiency of the proposed methods. 相似文献
155.
Gromer A Rawiso M Maaloum M 《Langmuir : the ACS journal of surfaces and colloids》2008,24(16):8950-8953
We have used atomic force microscopy to study the morphology of hydrophobic polyelectrolytes adsorbed on surfaces. The polyelectrolytes consisted of polystyrene sulfonate (PSS) chains made with three charge densities: 32%, 67%, and 92%. They were adsorbed on two types of surfaces: mica, and phospholipid bilayers made of mixed neutral and cationic lipids. We show that the chains with a low charge density (32%) are collapsed in spherical globules while highly charged chains (67% and 92%) are fully extended. End-to-end distances and contour lengths of the extended chains were measured. Statistical analysis shows that the persistence length of these chains depends on the surface where they adsorb. On lipid bilayers, highly ordered monolayers are formed upon increase of the proportion of cationic phospholipids. These results show that highly charged PSS chains behave in a similar manner than the stiffer, hydrophilic DNA when adsorbed on surfaces. It could lead to the design of new types of nanostructured surfaces using polyelectrolyte molecules synthesized with specific properties. 相似文献
156.
M Breton L Delemotte A Silve LM Mir M Tarek 《Journal of the American Chemical Society》2012,134(34):13938-13941
The use of small interfering RNA (siRNA) is a blossoming technique for gene regulation. However, its therapeutic potential is today severely hampered by the lack of an efficient means of safely delivering these nucleic acids to the intracellular medium. We report here that a single 10 ns high-voltage electric pulse can permeabilize lipid vesicles and allow the delivery of siRNA to the cytoplasm. Combining experiments and molecular dynamics simulations has allowed us to provide the detailed molecular mechanisms of such transport and to give practical guidance for the design of protocols aimed at using nanosecond-pulse siRNA electro-delivery in medical and biotechnological applications. 相似文献
157.
Investigation of the chemical modifications of beech wood lignin during heat treatment 总被引:3,自引:0,他引:3
Nicolas Brosse Roland El Hage Mounir Chaouch Mathieu Pétrissans Stéphane Dumarçay Philippe Gérardin 《Polymer Degradation and Stability》2010,95(9):1721-1528
Holocellulose, Klason lignin and milled wood lignin (MWL) of beech wood were extracted before and after heat treatment and analysed using CP MAS 13C NMR, 13C NMR, 31P NMR and size exclusion chromatography (SEC). Experimental results showed that the thermal treatment degrades hemicelluloses and affects lignin polymer through depolymerisation due mainly to cleavage of β-aryl-ether linkages and recondensation reactions. The spectroscopic analysis of MWL demonstrated that these recondensation reactions involved mainly guaiacyl units through formation of 5,5′-biphenolic and diarylmethane structures.Analysis of molecular weight distribution of MWL by SEC indicated that average molecular weights of heat treated milled wood lignin were lower than those of native milled wood lignin. 相似文献
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