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排序方式: 共有825条查询结果,搜索用时 15 毫秒
791.
Kevin Van holsbeeck Dr. Baptiste Fischer Dr. Simon Gonzalez Dr. Charlène Gadais Prof. Dr. Wim Versées Dr. José C. Martins Dr. Charlotte Martin Dr. Alexandre Wohlkönig Prof. Dr. Jan Steyaert Prof. Dr. Steven Ballet 《Angewandte Chemie (International ed. in English)》2023,62(24):e202219095
RAS proteins control various intracellular signaling networks. Mutations at specific locations were shown to stabilize their active guanosine triphosphate (GTP)-bound state, which is associated with the development of multiple cancers. An attractive approach to modulate RAS signaling is through its regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1). With the recent discovery of Nanobody14 (Nb14), which potently enhances SOS1-catalyzed nucleotide exchange on RAS, we explored the feasibility of developing peptide mimetics by structurally mimicking the complementarity-determining region 3 (CDR3). Guided by a biochemical GEF assay and X-ray co-crystal structures, successive rounds of optimization and gradual conformational rigidification led to CDR3 mimetics showing half of the maximal activation potential of Nb14 with an EC50 value of 29 μM. Altogether, this study demonstrated that peptides able to modulate a protein-protein interaction can be obtained by structural mimicry of a Nb paratope. 相似文献
792.
Conn CE Ces O Squires AM Mulet X Winter R Finet SM Templer RH Seddon JM 《Langmuir : the ACS journal of surfaces and colloids》2008,24(6):2331-2340
In the past two decades, the geometric pathways involved in the transformations between inverse bicontinuous cubic phases in amphiphilic systems have been extensively theoretically modeled. However, little experimental data exists on the cubic-cubic transformation in pure lipid systems. We have used pressure-jump time-resolved X-ray diffraction to investigate the transition between the gyroid QGII and double-diamond QDII phases in mixtures of 1-monoolein in 30 wt % water. We find for this system that the cubic-cubic transition occurs without any detectable intermediate structures. In addition, we have determined the kinetics of the transition, in both the forward and reverse directions, as a function of pressure-jump amplitude, temperature, and water content. A recently developed model allows (at least in principle) the calculation of the activation energy for lipid phase transitions from such data. The analysis is applicable only if kinetic reproducibility is achieved, at least within one sample, and achievement of such kinetic reproducibility is shown here, by carrying out prolonged pressure-cycling. The rate of transformation shows clear and consistent trends with pressure-jump amplitude, temperature, and water content, all of which are shown to be in agreement with the effect of the shift in the position of the cubic-cubic phase boundary following a change in the thermodynamic parameters. 相似文献
793.
794.
Willans CE Fish C Green M Kilby RJ Lynam JM Russell CA Whitwood AC 《Dalton transactions (Cambridge, England : 2003)》2008,(26):3422-3428
Substitution of Cl(-) in the tricyclic triphosphorus cage Cl(P(1))-P3(CBu(t))2 by a range of both anionic and neutral nucleophiles has been investigated. With anionic nucleophiles, reaction with fluoride and hydride anion was shown to afford F(P(1))-P3(CBu(t)) and H(P(1))-P3(CBu(t))2 respectively. Subsequent deprotonation of the latter results in the formation of the aromatic anion [1,2,4-P3(CBu(t))2]-. With neutral nucleophiles, addition of either PMe3 or PEt3 to Cl(P(1))-P3(CBu(t))2 in the presence of TlOTf results in the formation of the phosphine-phosphenium complexes [(R3P(P(1))-P3(CBu(t))2][OTf] (R = Me or Et): the structure of the methyl-substituted compound was determined by a single crystal X-ray diffraction study. The phosphine ligand in these complexes is extremely labile and addition of I2 to [(Me3P(P(1))-P3(CBu(t))2]+ results in the formation of I(P(1))-P3(CBu(t))2. 相似文献
795.
Simmel F Soukup J Zoerner A Radke J Kloft C 《Analytical and bioanalytical chemistry》2008,392(3):479-488
Voriconazole is a very potent antifungal agent used to treat serious fungal infections (candidiasis); it is also the therapy
of choice for aspergillosis. After standard dosing, several factors affect exposure of voriconazole, resulting in large variability
and demanding further elucidation of drug distribution. For measurements at the site of action, microdialysis is considered
to be an outstanding minimally invasive method. For determination of voriconazole in microdialysate and human plasma a new,
efficient, reliable, and robust HPLC assay using UV detection at 254 nm has been developed and validated. After simple sample
preparation using acetonitrile for plasma and for microdialysate, 20 μL were injected and separated on an RP-18 column. The
chromatographic run time was less than 4 min. Overall, the assay showed high precision (CV 93.9 to 99.5%) and accuracy (RE
−96.7 to +107%) for both matrices. Of the 36 drug products typically co-administered with voriconazole, none except ambroxol
interfered with its peak signal, and this interference was successfully managed. In summary, the method is highly suitable
for application in (pre)clinical microdialysis studies, e.g., of critically ill patients with invasive mycoses.
Figure Microdialysis probe situated in the interstitial space fluid containing voriconazole drug molecules (magenta coloured) extracting
an important target site representative matrix (microdialysate) [Courtesy of CMA] 相似文献
796.
The spectroscopy and dynamics of protonated methane have been of long-standing interest due to the unusual and highly fluxional behavior of CH5+. This reflects the fact that the ground-state wave function for CH5+ has nearly equal amplitude at the 120 equivalent minima and at the saddle points that connect these minima. While low-resolution spectra of CH5+ have been assigned, the nature of the couplings between the CH stretches and the low-frequency modes is not as well characterized. An understanding of this will be important in the interpretation of rotationally resolved spectra. In this work, fixed-node diffusion Monte Carlo techniques are used to calculate energies and probability amplitudes for several excited states. The calculated energies are shown to be in good agreement with previously reported vibrational configuration interactions calculations. Analysis of the 12-dimensional probability amplitudes shows that there are strong couplings between the high-frequency CH stretch and HCH bend motions and the low-frequency modes that lead to isomerization CH5+. 相似文献
797.
Effect of temperature on the sorption of europium on alumina: microcalorimetry and batch experiments
Morel JP Marmier N Hurel C Morel-Desrosiers N 《Journal of colloid and interface science》2012,376(1):196-201
The determination of enthalpies of reactions (aqueous and surface complexation) is used in this work to model the temperature effect on the adsorption processes. Microcalorimetry experiments were carried out to determine the enthalpy of adsorption of europium on γ-alumina at 25 °C. The stability constants at 50 °C were then calculated with the van't Hoff equation, and a 2-pK approach was used to model the adsorptive behavior of Eu on alumina at 50 °C, as a function of pH. The results have shown that the adsorption of Eu(3+) on the alumina surface is weakly endothermic. In the experimental conditions considered in the present study, the temperature has only a small effect on the adsorption reaction. 相似文献
798.
Averre CE Coles MP Crossley IR Day IJ 《Dalton transactions (Cambridge, England : 2003)》2012,41(1):278-284
The triphosphanes RMe(2)SiCH(2)P(PR'(2))(2) (R = Me, Ph; R' = SiMe(3), Cy) are synthesised in good yield via metathesis of organodichlorophosphanes and LiPR'(2), while for R' = Ph a propensity to form (Ph(2)P)(2) precludes isolation of the in situ characterised triphosphanes. Where R = Me and R' = SiMe(3) the triphosphane has also been characterised by single crystal X-ray diffraction and exhibits a single geometric conformer in the solid state, though solution-phase NMR spectra are indicative of facile conformational exchange across a wide temperature range. All of the described triphosphanes exhibit comparable behaviour, with their respective (31)P{(1)H} NMR spectra manifesting anomalous 'second-order' characteristics, which are considered using full spin-Hamiltonian simulation. Preliminary studies of coordination chemistry and ancillary reactivity of the triphosphanes are described. 相似文献
799.
Natan J. W. Straathof Charlotte B. Magnus Fedor Zhuravlev Andreas I. Jensen 《Molecules (Basel, Switzerland)》2021,26(15)
The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS4 macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS4 in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions. 相似文献
800.
Dimethylarsinic acid (DMA) is an organoarsenical compound that, along with monomethylarsonic acid, poses a health and an environmental risk, and a challenge to the energy industry. Little is known about the surface chemistry of DMA at the molecular level with materials relevant to geochemical environments and industrial sectors. We report herein the first in situ and surface-sensitive rapid kinetic studies on the adsorption and desorption of DMA to/from hematite and goethite at pH 7 and I = 0.01 M KCl using ATR-FTIR. Values for the apparent rates of adsorption and desorption were extracted from experimental data as a function of spectral components, flow rate of the aqueous phase, film thickness of hematite, and using chloride and hydrogen phosphate as desorbing agents. The adsorption kinetic data show fast and slow rates, consistent with the formation of more than one type of adsorbed DMA. Apparent adsorption and desorption rate constants were extracted from the dependency of the initial adsorption rates on [DMA(aq)]. Desorption rate constants were also extracted from desorption experiments using hydrogen phosphate and chloride solutions, and were found to be higher by 1-2 orders of magnitude than those using chloride. In light of the complex ligand exchange reaction mechanism of DMA desorption by phosphate species at pH 7, apparent desorption rate constants were found to depend on [hydrogen phosphate] with an order of 0.3. The impact of our studies on the environmental fate of DMA in geochemical environments, and the design of technologies to reduce arsenic content in fuels is discussed. 相似文献