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Our study was designed to examine how components of complex mixtures can
inhibit the binding of other components to receptor sites in the olfactory
system of the spiny lobster Panulirus argus. Biochemical binding assays
were used to study how two- to six-component mixtures inhibit binding of
the radiolabeled odorants taurine, L-glutamate and
adenosine-5'-monophosphate to a tissue fraction rich in dendritic membrane
of olfactory receptor neurons. Our results indicate that binding inhibition
by mixtures can be large and is dependent on the nature of the odorant
ligand and on the concentration and composition of the mixture. The binding
inhibition by mixtures of structurally related components was generally
predicted using a competitive binding model and binding inhibition data for
the individual components. This was not the case for binding inhibition by
most mixtures of structurally unrelated odorants. The binding inhibition
for these mixtures was generally smaller than that for one or more of their
components, indicating that complex binding interactions between components
can reduce their ability to inhibit binding. The magnitude of binding
inhibition was influenced more by the mixture's precise composition than by
the number of components in it, since mixtures with few components were
sometimes more inhibitory than mixtures with more components. These
findings raise the possibility that complex binding interactions between
components of a mixture and their receptors may shape the output of
olfactory receptor neurons to complex mixtures.
相似文献
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Optimized blood cell profiling method for genomic biomarker discovery using high-density microarray 总被引:1,自引:0,他引:1
J. Shou C. Dotson H. -R. Qian W. Tao C. Lin F. Lawrence M. N'Cho N. H. Kulkarni C. M. Bull L. M. Gelbert J. E. Onyia 《Biomarkers》2005,10(4):310-320
High-quality biomarkers for disease progression, drug efficacy and toxicity liability are essential for improving the efficiency of drug discovery and development. The identification of drug-activity biomarkers is often limited by access to and the quantity of target tissue. Peripheral blood has increasingly become an attractive alternative to tissue samples from organs as source for biomarker discovery, especially during early clinical studies. However, given the heterogeneous blood cell population, possible artifacts from ex vivo activations, and technical difficulties associated with overall performance of the assay, it is challenging to profile peripheral blood cells directly for biomarker discovery. In the present study, Applied BioSystems' blood collection system was evaluated for its ability to isolate RNA suitable for use on the Affymetrix microarray platform. Blood was collected in a TEMPUS tube and RNA extracted using an ABI-6100 semi-automated workstation. Using human and rat whole blood samples, it was demonstrated that the RNA isolated using this approach was stable, of high quality and was suitable for Affymetrix microarray applications. The microarray data were statistically analysed and compared with other blood protocols. Minimal haemoglobin interference with RNA labelling efficiency and chip hybridization was found using the TEMPUS tube and extraction method. The RNA quality, stability and ease of handling requirement make the TEMPUS tube protocol an attractive approach for expression profiling of whole blood to support target and biomarker discovery. 相似文献
107.
Alvaro CD Faria Agnaldo J Lopes José M Jansen Pedro L Melo 《Biomedical engineering online》2009,8(1):22-10
Background
Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases. Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects. 相似文献108.
Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin 总被引:3,自引:2,他引:1 下载免费PDF全文
LR Phillips CD Cole RJ Hendershot M Cotten TA Cross DD Busath 《Biophysical journal》1999,77(5):2492-2501
Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance. 相似文献
109.
S. S. Bhagwat D. M. Roland A. J. Main C. Gude K. Grim R. Goldstein D. S. Cohen R. Dotson J. Mathis W. Lee 《Bioorganic & medicinal chemistry letters》1992,2(12):1623-1626
Arylsulfonylamino arylalkanoic acids substituted with a pyridinylalkyl group on the arylalkanoic acid portion of the molecule were synthesized and found to behave as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs). One of these compounds (11), with a 1,3,5-trisubstituted central aromatic ring was demonstrated to have good functional bioavailability and efficacy as a platelet inhibitor in guinea pigs. 相似文献
110.