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111.
It was predicted that because the ear is spectrally tuned, it should be most affected by intense impulses with spectral peaks near the frequency where it is tuned best (3.0 kHz for the human ear) and progressively less affected by impulses at lower frequencies [G.R. Price, Scand. Audiol. Suppl. 16, 111-121 (1982)]. This prediction is counter to all the DRCs for impulse noise; therefore an adequate test is essential. In order to augment the data on hearing loss to low-spectral-frequency impulses, three groups of cats (eight, nine, and ten animals) were exposed on one occasion to 50 impulses from a 105-mm howitzer at peak SPLs of 153, 159, and 166 dB. Threshold shifts were measured electrophysiologically on the day of exposure (CTS) and following a 2-month recovery period (PTS). Maximum PTSs appeared at 4 kHz (even though the spectral peak of the impulse had been at about 100 Hz), and CTSs recovered into PTSs about half as large. Furthermore, for group data, even small CTSs tended to have a permanent component. These data raise the question as to whether or not any threshold shift persisting an hour or two after exposure to high levels should be considered tolerable. When compared with data from rifle fire exposures, the data confirmed the earlier prediction that as the spectral frequency drops, hazard declines at the rate of a little more than 3 dB/oct, contrary to the rating by existing DRCs.  相似文献   
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Asparagine glycosylation is one of the most common and important post-translational modifications of proteins in eukaryotic cells. N-glycosylation occurs when a triantennary glycan precursor is transferred en bloc to a nascent polypeptide (harboring the N-X-T/S sequon) as the peptide is cotranslationally translocated into the endoplasmic reticulum (ER). In addition to facilitating binding interactions with components of the ER proteostasis network, N-glycans can also have intrinsic effects on protein folding by directly altering the folding energy landscape. Previous work from our laboratories (Hanson et al. Proc. Natl. Acad. Sci. U.S.A. 2009, 109, 3131-3136; Shental-Bechor, D.; Levy, Y. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 8256-8261) suggested that the three sugar residues closest to the protein are sufficient for accelerating protein folding and stabilizing the resulting structure in vitro; even a monosaccharide can have a dramatic effect. The highly conserved nature of these three proximal sugars in N-glycans led us to speculate that introducing an N-glycosylation site into a protein that is not normally glycosylated would stabilize the protein and increase its folding rate in a manner that does not depend on the presence of specific stabilizing protein-saccharide interactions. Here, we test this hypothesis experimentally and computationally by incorporating an N-linked GlcNAc residue at various positions within the Pin WW domain, a small β-sheet-rich protein. The results show that an increased folding rate and enhanced thermodynamic stability are not general, context-independent consequences of N-glycosylation. Comparison between computational predictions and experimental observations suggests that generic glycan-based excluded volume effects are responsible for the destabilizing effect of glycosylation at highly structured positions. However, this reasoning does not adequately explain the observed destabilizing effect of glycosylation within flexible loops. Our data are consistent with the hypothesis that specific, evolved protein-glycan contacts must also play an important role in mediating the beneficial energetic effects on protein folding that glycosylation can confer.  相似文献   
115.

Background

The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances), is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures). Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one.

Results

This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online.

Conclusions

The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.
  相似文献   
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Concern about effects of anthropogenic noise on marine life has stimulated new studies to establish present-day ocean noise levels and compare them to noise levels from previous times. This paper reports on the trend in low-frequency (10-400 Hz) ambient noise levels and presents measurements made using a calibrated multi-element volume array at deep ocean sites in the Northeast Pacific from 1978 to 1986. The experiments provided spectral noise levels as well as horizontal and vertical noise directionality. The data presented here provide evidence that the trend derived from 1960s data extended to around 1980, but has since continued at a lower rate.  相似文献   
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This discussion puts a case of advocatus diaboli: that the Treaty of the Metre, its associated administrative apparatus and the International System of measurement units (SI) has basically failed for chemical measurement and is largely irrelevant to modern analysis, much of practical measurement in modern economies and much of recent technology. The practical use of the chemical unit termed the mole, the introduction to the SI units of the thermodynamic mole and the invention of a new physical quantity called “amount of substance” are each reviewed with the conclusion that the current means of expressing the results of chemical measurements are unsatisfactory in both practice and theory and are imposing large and readily avoidable costs on all advanced economies.  相似文献   
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A three-dimensional full-Stokes computational model is considered for determining the dynamics,temperature,and thickness of ice sheets.The goveming thermomechanical equations consist of the three-dimensional full-Stokes system with nonlinear rheology for the momentum,an advective-diffusion energy equation for temperature evolution,and a mass conservation equation for ice-thickness changes.Here,we discuss the variable resolution meshes,the finite element discretizations,and the parallel algorithms employed by the model components.The solvers are integrated through a well-designed coupler for the exchange of parametric data between components.The discretization utilizes high-quality,variable-resolution centroidal Voronoi Delaunay triangulation meshing and existing parallel solvers.We demonstrate the gridding technology,discretization schemes,and the efficiency and scalability of the parallel solvers through computational experiments using both simplified geometries arising from benchmark test problems and a realistic Greenland ice sheet geometry.  相似文献   
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Common industrial procedures often expose polymers to liquids and vapors which may affect their thermal properties. By carrying out thermoanalytical measurements under simulated process conditions, the scientist can investigate environmental effects on the properties of the material. Such experiments can also be used to demonstrate the nature of processes taking place. This work illustrates case studies regarding the application of thermogravimetry, thermomechanical, dynamic mechanical and dielectric measurements to monitor the behaviour of fibers, films and adhesives under such conditions.  相似文献   
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