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31.
We report the development of novel reagents and approaches for generating recyclable biosensors. The use of aqueous media for the formation of protein binding alkylthiolate monolayers on Au surfaces results in accelerated alkylthiolate monolayer formation and improvement in monolayer integrity as visualized by fluorescence microscopy and CV techniques. We have also developed an electrocleaning protocol that is compatible with microfluidics devices, and this technique serves as an on-chip method for cleaning Au substrates both before and after monolayer formation. The techniques for the formation and dissociation of biotinylated SAMs from aqueous solvents reported here may be applied towards the development of Au-based sensor devices and microfluidics chips in the future. A potential use of these devices includes the specific capture and triggered release of target cells, proteins, or small molecules from liquid samples.  相似文献   
32.
We report on two-dimensional computer simulations of frictionless granular packings at various area fractions φ above the jamming point φ(c). We measure the anisotropy in coarse-grained stress ε(s) and shear modulus ε(m) as functions of coarse-graining scale, R. ε(s) can be collapsed onto a master curve after rescaling R by a characteristic length scale ξ and ε(s) by an anisotropy magnitude A. Both A and ξ accelerate as φ→φ(c) from above, consistent with a divergence at φ(c). ε(m) shows no characteristic length scale and has a nontrivial power-law form, ε(m)~R(-0.62), over almost the entire range of R at all φ. These results suggest that the force chains present in the spatial structure of the quenched stress may be governed by different physics than the anomalous elastic response near jamming.  相似文献   
33.
A concise and efficient one-pot synthesis of functionalized sulfonylated pyridines via an S(N)Ar reaction of readily available pyridines and sodium sulfinate salts in the presence of tetrabutylammonium chloride is presented.  相似文献   
34.
Ubiquitin-specific proteases (USPs) have in recent years emerged as a promising therapeutic target class. We identified selective small-molecule inhibitors against a deubiquitinase complex, the human USP1/UAF1, through quantitative high throughput screening (qHTS) of a collection of bioactive molecules. The top inhibitors, pimozide and GW7647, inhibited USP1/UAF1 noncompetitively with a K(i) of 0.5 and 0.7?μM, respectively, and displayed selectivity against a number of deubiquitinases, deSUMOylase, and cysteine proteases. The USP1/UAF1 inhibitors act synergistically with cisplatin in inhibiting cisplatin-resistant non-small cell lung cancer (NSCLC) cell proliferation. USP1/UAF1 represents a promising target for drug intervention because of its involvement in translesion synthesis and Fanconi anemia pathway?important for normal DNA damage response. Our results support USP1/UAF1 as a potential therapeutic target and provide an example of targeting the USP/WD40 repeat protein complex for inhibitor discovery.  相似文献   
35.
36.
Raf, a threonine/serine kinase in the Raf/MEK/ERK pathway, regulates cell proliferation. Raf''s full activation requires dimerization. Aberrant activation through dimerization is an important therapeutic target. Despite its clinical importance, fundamental questions, such as how the side-to-side dimerization promotes the OFF-to-ON transition of Raf''s kinase domain and how the fully activated ON-state kinase domain is stabilized in the dimer for Raf signaling, remain unanswered. Herein, we decipher an atomic-level mechanism of Raf activation through dimerization, clarifying this enigma. The mechanism reveals that the replacement of intramolecular π–π stacking by intermolecular π–π stacking at the dimer interface releases the structural constraint of the αC-helix, promoting the OFF-to-ON transition. During the transition, the inhibitory hydrophobic interactions were disrupted, making the phosphorylation sites in A-loop approach the HRD motif for cis-autophosphorylation. Once fully activated, the ON-state kinase domain can be stabilized by a newly identified functional N-terminal basic (NtB) motif in the dimer for Raf signaling. This work provides atomic level insight into critical steps in Raf activation and outlines a new venue for drug discovery against Raf dimerization.

We decipher an atomic-level mechanism of Raf activation through dimerization, revealing that the disruption of intramolecular π–π stacking at the dimer interface promotes the OFF-to-ON transition.  相似文献   
37.
Rate constants for the low-pressure unimolecular decomposition of ONBr and ONCl in an argon bath have been determined at temperatures in the vicinity of 1000°K. Both molecules exhibit the usual depression of the observed activation energy below the bond dissociation energy. The Arrhenius expressions obtained are (units of cc mole?1 sec?1): Treatment of the data by the classical RRK theory yields s ? 2.7 ± 1 for ONCl and 3.0 ± 0.6 for ONBr. Coupling the shock tube results for ONCl with lower-temperature data from Ashmore and Burnett [3], one obtains s ? 2.5 ± 0.5 and λ ≈? 1. If it is assumed that s is also 2.5 for ONBr, then one finds the surprising (but tentative) result that λONCl? Ar/λONBr? Ar ≈? 3 to 4.  相似文献   
38.
Direct measurements of the flux-flow resistance of Pb-In alloys nearH c2 confirm the theory of Thompson and of Takayama and Ebisawa in the temperature regionT/T c=0.2–0.7. AboveT/T c=0.7 the experimental results show significant deviations and seem to extrapolate forT/T c=1 to the theories of Schmid and of Caroli and Maki. The problems encountered by previous experimentators, whose results were in qualitative agreement with the theory of Caroli and Maki, are discussed.  相似文献   
39.
Capillary electrochromatography (CEC) continues to captivate many separation scientists. A remarkable activity is apparent from the numerous publications in the literature using CEC. A review of the most recent progress in CEC is presented herein, covering an extensive fraction of the literature on CEC published from the year 1997 until the beginning of 2000. Most of the recent developments have concentrated on column technology.  相似文献   
40.
The curvature seen in Child's law plots of current-voltage characteristics measured using plane parallel diodes may be analysed in a number of ways to give information about the work function distribution of a cathode. This paper suggests a simple technique for characterising a cathode based on the assumption it has a “top-hat” work function distribution. The technique allows synthetic current/voltage characteristics to be generated which agree well with the practical characteristics from which the parameters of the work function distribution were derived. The parameters of the “top-hat” model may also be used to obtain an equivalent Gaussian work function distribution which gives almost identical synthetic characteristics and Schottky enhancement may be modelled in a rather empirical manner. Since either model gives good predictions, synthetic characteristics may be used to investigate other methods used to characterise cathodes. It is found that there is generally reasonable agreement which could be improved, for most practical work function distributions, by the choice of parameters slightly different from those normally used.  相似文献   
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