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221.
Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data.  相似文献   
222.
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 /) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 / mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 / mice. Testosterone levels were higher after BC supplementation only in Bcmo1 / mice, which had, unlike wild-type (Bcmo1 +/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.  相似文献   
223.
The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations.  相似文献   
224.
An ultrametric topology formalizes the notion of hierarchical structure. An ultrametric embedding, referred to here as ultrametricity, is implied by a hierarchical embedding. Such hierarchical structure can be global in the data set, or local. By quantifying extent or degree of ultrametricity in a data set, we show that ultrametricity becomes pervasive as dimensionality and/or spatial sparsity increases. This leads us to assert that very high dimensional data are of simple structure. We exemplify this finding through a range of simulated data cases. We discuss also application to very high frequency time series segmentation and modeling.  相似文献   
225.
Several vanadium compounds have been known for the hypoglycemic and anticancer effects. However, the mechanisms of the pharmacological and toxicological effects were not clear. In this work, we in- vestigated the potential targets of vanadium in mitochondria. Vanadyl ions were found to bind to mi- tochondria from rat liver with a stoichiometry of 244±58 nmol/mg protein and an apparent dissocia- tion constant (Kd) of (2.0±0.8)×10·16 mol/L. Using size exclusion chromatography, a vanadium-binding protein was isolated and identified to be the 60-kDa heat shock protein (HSP60) by mass spectrometry analysis and immunoassays. Additionally, binding of vanadyl ions was found to result in depolymeri- zation of homo-oligomeric HSP60 (GroEL). HSP60 is an indispensable molecular chaperone and in- volved in many kinds of pathogenesis of inflammatory and autoimmune diseases, e.g. type 1 diabetes. Our results suggested that HSP60 could be a novel important target involved in the biological and/or toxicological effects of vanadium compounds.  相似文献   
226.
In this paper, we design and fabricate a 3D scaffold using rapid prototyping (RP) technology for tissue engineering. The scaffold should have a three-dimensional interconnected pore network. We fabricate a polycaprolactone (PCL) scaffold with interconnecting pores and uniform porosity for cell ingrowth using a 3D plotting system. In order to keep the three dimensional shape under mechanical loading while implanted, we design an oscillating nozzle system to increase elastic modulus and yield strength of PCL ...  相似文献   
227.
228.
X-ray powder diffraction is an indispensable technique to study material structure, phase transition and so on. It is necessary for high quality diffraction data to get high-precision diffraction angle. This work proposed four corrected functions of X-ray powder diffraction angle. Two methods, linearization method and modified Levenberg-Marquardt iteration method, are given to solve the function parameters, and the modified Levenberg-Marquardt method has fast convergent speed and stable solution. Two methods can give closed parameters, including those of Lu, Liu, and Chu functions and polynomial. New-corrected functions were used to fit the diffraction angle error of the tetragonal rutile polycrystalline TiO2 mixed with Gd0.45Y2.55Sc2Ga3O12 as a standard sample, and the computation result indicates that these functions can characterize the diffraction error very well. In some cases, the new-corrected functions can describe the diffraction angle error better than the reported corrected functions. At the same time, the lattice parameter of Gdo.45Y2.55Sc2Ga3O12 was computed with two methods. When the corrected function parameters and lattice parameters were solved by the least square method, the interaction of the function parameters and lattice parameters would result in great error. However, when the X-ray diffraction angles were corrected by corrected functions using a standard sample, the authentic lattice parameters can be obtained by the least square fitting.  相似文献   
229.
Solar-driven high temperature radiant cooling   总被引:1,自引:0,他引:1  
Solar energy is widely used as one of the most important renewable energy. In addition to the growing applications of solar PV and solar water heater, solar cooling is also considered very valuable and the related researches are developing fast because of the synchronism between solar irradiance and building cooling load. Current studies mainly focus on the high temperature solar collector technique and heat-driven cooling technique, while little concern has been paid to the transport process of cooling power. In this paper, the high temperature radiant cooling is studied as an alternative way for transporting cooling power, and the performance of the combination of radiant ceiling and solar cooling is also studied. From simulation and theoretical analysis results, high temperature radiant cooling terminal shows better cooling power transportation ability against conventional air-conditioning terminal, and its thermal comfort is improved. Experiment results indicate that radiant cooling can enhance the chiller’s COP (Coefficient of Performance) by 17% and cooling power regeneration by 50%. According to analysis in this paper, high temperature radiant cooling is proved to be suitable for solar cooling system, and out work can serve as a reference for later system design and promotion. Supported by the National Natural Science Foundation of China (Grant No. 50876064)  相似文献   
230.
Density functional theory (DFT) study of reaction between vanadium trioxide cluster cation (VO3^+) and ethylene (C2H4) to yield VO2^+ + CH3CHO (acetaldehyde) and VO2CH2^+ + HCHO (formaldehyde) is carried out. Structures of all reactants, products, intermediates, and transition state in the reaction have been optimized and characterized. The results show unexpected barriers in the reaction due to the existence of a η^2-O2 moiety in the ground state structure of VO3^+. The initial reaction steps combining ethylene adsorption, C=C activation and O-O cleavage are proposed as rate limiting processes. Comparison of reactions of VO3^+ + C2H4 with VO3 + C2H4 and VO2^+ + C2H4 in the previous studies is made in detail. The results of this work may shed light on the understanding of C=C bond cleavage in related heterogeneous catalysis.  相似文献   
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