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Tomasz Maciej Stepniewski Arturo Mancini Richard gren Mariona Torrens-Fontanals Meriem Semache Michel Bouvier Kristoffer Sahlholm Billy Breton Jana Selent 《Chemical science》2021,12(33):10990
Brain functions rely on neurotransmitters that mediate communication between billions of neurons. Disruption of this communication can result in a plethora of psychiatric and neurological disorders. In this work, we combine molecular dynamics simulations, live-cell biosensor and electrophysiological assays to investigate the action of the neurotransmitter dopamine at the dopaminergic D2 receptor (D2R). The study of dopamine and closely related chemical probes reveals how neurotransmitter binding translates into the activation of distinct subsets of D2R effectors (i.e.: Gi2, GoB, Gz and β-arrestin 2). Ligand interactions with key residues in TM5 (S5.42) and TM6 (H6.55) in the D2R binding pocket yield a dopamine-like coupling signature, whereas exclusive TM5 interaction is typically linked to preferential G protein coupling (in particular GoB) over β-arrestin. Further experiments for serotonin receptors indicate that the reported molecular mechanism is shared by other monoaminergic neurotransmitter receptors. Ultimately, our study highlights how sequence variation in position 6.55 is used by nature to fine-tune β-arrestin recruitment and in turn receptor signaling and internalization of neurotransmitter receptors.Neurotransmitter contacts within the receptor binding site differentially contribute to the overall functional response: transmembrane helix (TM) 5 contacts promote G protein coupling whereas concerted TM5–TM6 contacts enhance β-arrestin recruitment. 相似文献
34.
We investigate the optimal filtering problem in the simplest Gaussian linear system driven by fractional Brownian motions.
At first we extend to this setting the Kalman–Bucy filtering equations which are well-known in the specific case of usual
Brownian motions. Closed form Volterra type integral equations are derived both for the mean of the optimal filter and the
variance of the filtering error. Then the asymptotic stability of the filter is analyzed. It is shown that the variance of
the filtering error converges to a finite limit as the observation time tends to infinity.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
35.
Laveissière G Todor L Degrande N Jaminion S Jutier C Di Salvo R Van Hoorebeke L Alexa LC Anderson BD Aniol KA Arundell K Audit G Auerbach L Baker FT Baylac M Berthot J Bertin PY Bertozzi W Bimbot L Boeglin WU Brash EJ Breton V Breuer H Burtin E Calarco JR Cardman LS Cavata C Chang CC Chen JP Chudakov E Cisbani E Dale DS de Jager CW De Leo R Deur A d'Hose N Dodge GE Domingo JJ Elouadrhiri L Epstein MB Ewell LA Finn JM Fissum KG Fonvieille H Fournier G Frois B Frullani S Furget C Gao H Gao J 《Physical review letters》2004,93(12):122001
We report a virtual Compton scattering study of the proton at low c.m. energies. We have determined the structure functions P(LL)-P(TT)/epsilon and P(LT), and the electric and magnetic generalized polarizabilities (GPs) alpha(E)(Q2) and beta(M)(Q2) at momentum transfer Q(2)=0.92 and 1.76 GeV2. The electric GP shows a strong falloff with Q2, and its global behavior does not follow a simple dipole form. The magnetic GP shows a rise and then a falloff; this can be interpreted as the dominance of a long-distance diamagnetic pion cloud at low Q2, compensated at higher Q2 by a paramagnetic contribution from piN intermediate states. 相似文献
36.
Poullet JB Sima DM Van Huffel S Van Hecke P 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2007,186(2):293-304
Accurate and efficient filtering techniques are required to suppress large nuisance components present in short-echo time magnetic resonance (MR) spectra. This paper discusses two powerful filtering techniques used in long-echo time MR spectral quantitation, the maximum-phase FIR filter (MP-FIR) and the Hankel-Lanczos Singular Value Decomposition with Partial ReOrthogonalization (HLSVD-PRO), and shows that they can be applied to their more complex short-echo time spectral counterparts. Both filters are validated and compared through extensive simulations. Their properties are discussed. In particular, the capability of MP-FIR for dealing with macromolecular components is emphasized. Although this property does not make a large difference for long-echo time MR spectra, it can be important when quantifying short-echo time spectra. 相似文献
37.
Anthony PL Arnold RG Band HR Borel H Bosted PE Breton V Cates GD Chupp TE Dietrich FS Dunne J Erbacher R Fellbaum J Fonvieille H Gearhart R Holmes R Hughes EW Johnson JR Kawall D Keppel C Kuhn SE Lombard-Nelsen RM Marroncle J Maruyama T Meyer W Meziani Z Middleton H Morgenstern J Newbury NR Petratos GG Pitthan R Prepost R Roblin Y Rock SE Rokni SH Shapiro G Smith T Souder PA Spengos M Staley F Stuart LM Szalata ZM Terrien Y Thompson AK White JL Woods M Xu J Young CC Zapalac G 《Physical review D: Particles and fields》1996,54(11):6620-6650
38.
d'Espinose de Lacaillerie JB Fretigny C Massiot D 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2008,192(2):244-251
Structural disorder at the scale of two to three atomic positions around the probe nucleus results in variations of the EFG and thus in a distribution of the quadrupolar interaction. This distribution is at the origin of the lineshape tailing toward high fields which is often observed in the MAS NMR spectra of quadrupolar nuclei in disordered solids. The Czjzek model provides an analytical expression for the joint distribution of the NMR quadrupolar parameters upsilon(Q) and eta from which a lineshape can be predicted. This model is derived from the Central Limit Theorem and the statistical isotropy inherent to disorder. It is thus applicable to a wide range of materials as we have illustrated for 27Al spectra on selected examples of glasses (slag), spinels (alumina), and hydrates (cement aluminum hydrates). In particular, when relevant, the use of the Czjzek model allows a quantitative decomposition of the spectra and an accurate extraction of the second moment of the quadrupolar product. In this respect, it is important to realize that only rotational invariants such as the quadrupolar product can make sense to describe the quadrupolar interaction in disordered solids. 相似文献
39.
Philippe Pinel Bertrand Thirion Sébastien Meriaux Antoinette Jobert Julien Serres Denis Le Bihan Jean-Baptiste Poline Stanislas Dehaene 《BMC neuroscience》2007,8(1):91
Background
Although cognitive processes such as reading and calculation are associated with reproducible cerebral networks, inter-individual variability is considerable. Understanding the origins of this variability will require the elaboration of large multimodal databases compiling behavioral, anatomical, genetic and functional neuroimaging data over hundreds of subjects. With this goal in mind, we designed a simple and fast acquisition procedure based on a 5-minute functional magnetic resonance imaging (fMRI) sequence that can be run as easily and as systematically as an anatomical scan, and is therefore used in every subject undergoing fMRI in our laboratory. This protocol captures the cerebral bases of auditory and visual perception, motor actions, reading, language comprehension and mental calculation at an individual level. 相似文献40.
Ralf Seemann Jean-Baptiste Fleury Corinna C. Maass 《The European physical journal. Special topics》2016,225(11-12):2227-2240
Self-propelled droplets are a special kind of self-propelled matter that are easily fabricated by standard microfluidic tools and locomote for a certain time without external sources of energy. The typical driving mechanism is a Marangoni flow due to gradients in the interfacial energy on the droplet interface. In this article we review the hydrodynamic prerequisites for self-sustained locomotion and present two examples to realize those conditions for emulsion droplets, i.e. droplets stabilized by a surfactant layer in a surrounding immiscible liquid. One possibility to achieve self-propelled motion relies on chemical reactions affecting the surface active properties of the surfactant molecules. The other relies on micellar solubilization of the droplet phase into the surrounding liquid phase. Remarkable cruising ranges can be achieved in both cases and the relative insensitivity to their own ‘exhausts’ allows to additionally study collective phenomena. 相似文献