全文获取类型
收费全文 | 257篇 |
免费 | 11篇 |
专业分类
化学 | 184篇 |
力学 | 5篇 |
数学 | 25篇 |
物理学 | 54篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 14篇 |
2012年 | 10篇 |
2011年 | 21篇 |
2010年 | 21篇 |
2009年 | 19篇 |
2008年 | 17篇 |
2007年 | 13篇 |
2006年 | 17篇 |
2005年 | 16篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 12篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有268条查询结果,搜索用时 31 毫秒
31.
Background
Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis—a chronic, painful bladder disease. APF inhibits the proliferation of normal bladder epithelial cells and cancer cells in vitro, presumably by binding to its cellular receptor, cytoskeleton associated-protein 4 (CKAP4); however, the biophysical interaction of APF with CKAP4 has not been characterized previously. In this study, we used surface plasmon resonance (SPR) to explore the binding kinetics of the interaction of APF and as-APF (a desialylated APF analogue with full activity) to CKAP4.Results
We immobilized non-glycosylated APF (TVPAAVVVA) to the Fc1 channel as the control and as-APF to Fc2 channel as the ligand in order to measure the binding of CKAP4 recombinant proteins encompassing only the extracellular domain (Aa 127–602) or the extracellular domain plus the transmembrane domain (Aa 106–602). Positive binding was detected to both CKAP4126–602 and CKAP4106–602, suggesting that as-APF can bind specifically to CKAP4 and that the potential binding site(s) are located within the extracellular domain. To identify the primary APF binding site(s) within the CKAP4 extracellular domain, deletion mutants were designed according to structural predictions, and the purified recombinant proteins were immobilized on a CM5 chip through amine-coupling to measure as-APF binding activity. Importantly, both CKAP4127–360 and CKAP4361–524 exhibited a fast association rate (k on ) and a slow dissociation rate (k off ), thus generating high binding affinity and suggesting that both regions contribute relatively equally to overall as-APF binding. Therefore, two or more as-APF binding sites may exist within the Aa 127–524 region of the CKAP4 extracellular domain.Conclusions
We determined that the CKAP4127–360 and CKAP4361–524 mutants exhibit improved binding activity to as-APF as compared to the full-length extracellular domain, making it possible to detect low concentrations of as-APF in urine, thereby establishing a foundation for a non-invasive diagnostic assay for IC. Further, these data have revealed novel APF binding site(s) suggesting that targeting this region of CKAP4 to inhibit APF binding may be a useful strategy for treating IC-related bladder pathology.32.
Ribeiro da Silva MA Lobo Ferreira AI Cimas Á 《The Journal of organic chemistry》2011,76(10):3754-3764
Thermodynamic properties of 3- and 4-phenoxyphenol have been determined by using a combination of calorimetric and effusion techniques as well as by high-level ab initio molecular orbital calculations. The standard (p° = 0.1 MPa) molar enthalpies of formation in the condensed and gas states, Δ(f)H(m)°(cr or l) and Δ(f)H(m)°(g), at T = 298.15 K, of 3- and 4-phenoxyphenol were derived from their energies of combustion in oxygen, measured by a static bomb calorimeter, and from the enthalpies of vaporization or sublimation derived respectively by Calvet microcalorimetry for the 3-phenoxyphenol and by Knudsen effusion technique for the 4-phenoxyphenol. The theoretically estimated gas-phase enthalpies of formation were calculated from high-level ab initio molecular orbital calculations at the G3(MP2)//B3LYP level of theory. Furthermore, this composite approach was also used to obtain information about the gas-phase acidities, gas-phase basicities, proton and electron affinities, adiabatic ionization enthalpies, and, finally, O?H bond dissociation enthalpies. The good agreement between the G3MP2B3-derived values and the experimental gas-phase enthalpies of formation for the 3- and 4-phenoxyphenol gives confidence to the estimate concerning the 2-phenoxyphenol isomer, which was not experimentally studied, and to the estimates concerning the radical and the anion. Additionally, the experimental values of gas-phase enthalpies of formation were also compared with estimates based on the empirical scheme developed by Cox. 相似文献
33.
We consider a periodically heterogeneous and perforated medium
filling an open domain Ω of ℝN. Assuming that the size of the periodicity of the structure and of the holes is O(ε),
we study the asymptotic behavior, as ε → 0, of the
solution of an elliptic boundary value problem with strongly oscillating coefficients posed in Ωε
(Ωε being Ω minus the holes) with a Neumann condition on the boundary of the holes. We use Bloch wave
decomposition to introduce an approximation of the solution in the
energy norm which can be computed from the homogenized solution
and the first Bloch eigenfunction. We first consider the case
where Ωis ℝN and then localize the problem for a
bounded domain Ω, considering a homogeneous Dirichlet
condition on the boundary of Ω. 相似文献
34.
We present two Valence Force Field models for sp 2 bonded carbon sheets with three and five parameters adjusted to the phonon frequencies of graphite. The transferability of the force constants is checked for the vibrations of C60, where we compare our results to other theoretical and experimental results. 相似文献
35.
36.
The polarization produced by the relative displacement of the potentials trapping two spin species of a dilute Fermi gas with N=N is calculated at unitarity by assuming phase separation between the superfluid and a polarized phase at zero temperature. Because of the energy cost associated with pair breaking, the dipole polarizability is strongly quenched and exhibits important deviations from the ideal gas behavior even for nonlinear displacements of the order of the size of the atomic cloud. The behavior in the presence of different trapping frequencies (monopole polarization) for the two spin species is also discussed. Our results suggest new experimental perspectives to explore the quantum phases of interacting Fermi gases. 相似文献
37.
Hybrid DFT/MM methods have been used to investigate the electronic and geometric properties of the microporous titanosilicate ETS-10. A comparison of finite length and periodic models demonstrates that band gap energies for ETS-10 can be well represented with relatively small cluster models. Optimization of finite clusters leads to different local geometries for bulk and end sites, where the local bulk TiO6 geometry is in good agreement with recent experimental results. Geometry optimizations reveal that any asymmetry within the axial O-Ti-O chain is negligible. The band gap in the optimized model corresponds to a O(2p) --> Tibulk(3d) transition. The results suggest that the three Ti atom, single chain, symmetric, finite cluster is an effective model for the geometric and electronic properties of bulk and end TiO6 groups in ETS-10. 相似文献
38.
Cardoso AS Marques MM Srinivasan N Prabhakar S Lobo AM Rzepa HS 《Organic & biomolecular chemistry》2006,4(21):3966-3972
Rearrangement of N(a)-prenyl-N(b)-acetyltryptamine, induced by BF3.Et2O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, N(a)-prenyl-N(b)-phthaloyl-l-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF3 to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol(-1). 相似文献
39.
de Melo JV Vasconcelos RH Furtado AF Peixoto CA Silva-Filha MH 《Micron (Oxford, England : 1993)》2008,39(8):1342-1350
The larvicidal action of the entomopathogen Bacillus sphaericus towards Culex quinquefasciatus is due to the binary (Bin) toxin present in crystals, which are produced during bacterial sporulation. The Bin toxin needs to recognize and bind specifically to a single class of receptors, named Cqm1, which are 60-kDa α-glucosidases attached to the apical membrane of midgut cells by a glycosylphosphatidylinositol anchor. C. quinquefasciatus resistance to B. sphaericus has been often associated with the absence of the α-glucosidase Cqm1 in larvae midgut microvilli. In this work, we aimed to investigate, at the ultrastructural level, the midgut cells from C. quinquefasciatus larvae whose resistance relies on the lack of the Cqm1 receptor. The morphological analysis showed that midgut columnar cells from the resistant larvae are characterized by a pronounced production of lipid inclusions, throughout the 4th instar. At the end of this stage, resistant larvae had an increased size and number of these inclusions in the midgut cells, while only a small number were observed in the cells from susceptible larvae. The morphological differences in the midgut cells of resistant larvae found in this work suggested that the lack of the Cqm1 receptor, which also has a physiological role as being an α-glucosidase, can be related to changes in the cell metabolism. The ultrastructural effects of Bin toxin on midgut epithelial cells from susceptible and resistant larvae were also investigated. The cytopathological alterations observed in susceptible larvae treated with a lethal concentration of toxin included breakdown of the endoplasmic reticulum, mitochondrial swelling, microvillar disruption and vacuolization. Some effects were observed in cells from resistant larvae, although those alterations did not lead to larval death, indicating that the receptor Cqm1 is essential to mediate the larvicidal action of the toxin.This is the first ultrastructural study to show differences in the cell morphology of resistant larvae and further investigation is needed to understand the impact of the lack of expression of midgut enzymes on the physiology of resistant insects. 相似文献
40.
Valquiria P. Andrade Mateus Mittersteiner Márcio M. Lobo Clarissa P. Frizzo Hélio G. Bonacorso Marcos A.P. Martins Nilo Zanatta 《Tetrahedron letters》2018,59(10):891-894
This study reports a comparison between conventional methods, ionic liquids, microwave (MW) irradiation, and combinations thereof for the synthesis of a series of fourteen 1-aryl-2-arylamino-5-trifluoroacetyl-1,2,3,4-tetrahydropyridines. In all of the reactions tested, the products were obtained at very good yields (87–97%), but the reaction times were very different, depending on the method used. Comparing to other methods, the time decreased to 1?min when [BMIM]BF4 under MW irradiation was used, thus evidencing a synergic effect. 相似文献