全文获取类型
收费全文 | 1731篇 |
免费 | 39篇 |
国内免费 | 15篇 |
专业分类
化学 | 945篇 |
晶体学 | 9篇 |
力学 | 56篇 |
数学 | 264篇 |
物理学 | 511篇 |
出版年
2021年 | 23篇 |
2020年 | 12篇 |
2019年 | 10篇 |
2018年 | 18篇 |
2017年 | 15篇 |
2016年 | 20篇 |
2015年 | 25篇 |
2014年 | 34篇 |
2013年 | 92篇 |
2012年 | 46篇 |
2011年 | 89篇 |
2010年 | 38篇 |
2009年 | 44篇 |
2008年 | 77篇 |
2007年 | 82篇 |
2006年 | 61篇 |
2005年 | 69篇 |
2004年 | 63篇 |
2003年 | 55篇 |
2002年 | 58篇 |
2001年 | 44篇 |
2000年 | 41篇 |
1999年 | 26篇 |
1998年 | 16篇 |
1997年 | 25篇 |
1996年 | 38篇 |
1995年 | 32篇 |
1994年 | 22篇 |
1993年 | 29篇 |
1992年 | 37篇 |
1991年 | 25篇 |
1990年 | 18篇 |
1989年 | 16篇 |
1988年 | 27篇 |
1987年 | 17篇 |
1986年 | 15篇 |
1985年 | 30篇 |
1984年 | 23篇 |
1983年 | 18篇 |
1982年 | 21篇 |
1981年 | 20篇 |
1980年 | 33篇 |
1979年 | 26篇 |
1978年 | 22篇 |
1977年 | 19篇 |
1976年 | 24篇 |
1975年 | 23篇 |
1974年 | 17篇 |
1973年 | 27篇 |
1972年 | 13篇 |
排序方式: 共有1785条查询结果,搜索用时 437 毫秒
941.
942.
Massah AR Dreiocker F Jackson RF Pickup BT Oomens J Meijer AJ Schäfer M 《Physical chemistry chemical physics : PCCP》2011,13(29):13255-13267
An extensive set of organozinc iodides, useful for Negishi-type cross-coupling reactions, are investigated as respective cations after formal loss of iodide in the gas phase. Firstly, two new alkylzinc compounds derived from Tyrosine (Tyr) and Tryptophan (Trp) are closely examined. Secondly, the influence of specific protecting groups on the subtle balance between intra- and intermolecular coordination of zinc in these reagents is probed through trifluoroacetyl (TFA)-derivatized alkylzinc compounds. Finally, the influence of the strongly coordinating bidentate ligand N,N,N',N'-tetramethylethylenediamine (TMEDA) on the structure of alkylzinc cations is further explored in order to better understand the stability of the respective complexes towards water. A combination of electrospray (ESI)-MS/MS, accurate ion mass measurements, infrared multiple-photon dissociation (IRMPD) spectroscopy and computational modelling allowed the full characterisation of all dimethylformamide (DMF)-solvated and TMEDA-coordinated alkylzinc cations in the gas phase. The calculations indicate that the zinc cation in gas-phase alkylzinc-DMF or TMEDA-complex ions preferentially adopts a tetrahedral coordination sphere with four ligands. Additionally, conformers with only three binding partners bound to zinc but with effectively combined hydrogen-bond interactions are also found. Collision induced dissociation (CID) patterns demonstrate that the zinc-DMF interaction in tetrahedral four-coordinate mono-DMF-zinc complex ions as well as the interaction between TMEDA and zinc in the corresponding complex ions is even stronger than typical covalent bonds. In most cases, all major features of the IRMPD spectra are consistent with only a single major isomer, allowing secured identification and assignment. 相似文献
943.
We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (?6 mm ×~550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (?6 mm × 40 μm) with a laser-drilled aperture (~100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations. 相似文献
944.
We report the development of a magnetically controlled drug delivery device for on-demand drug release to treat chronic diseases. The devices consist of drug-loaded micro-reservoirs (6 mm in diameter and ~550 μm in depth), sealed by magnetic PDMS (polydimethylsiloxane) membranes (? 6 mm × 40 μm) with laser-drilled apertures and actuated by an external magnetic field. We present a detailed analysis of the magnetic actuation forces and provide an estimate of the resulting membrane deflections. The reservoirs are fabricated by PDMS molding and loaded with drugs using solvent evaporation methods. Post-processing procedures using bovine serum albumin (BSA) adsorption on magnetic PDMS surfaces are carried out to modify the surface wettability and to allow water filling and dissolution of the drugs in the reservoirs. Detailed surface modification processes are described and characterized. The device demonstrates on-demand delivery of methylene blue (MB) as a model drug. Intermittent magnetic actuations of the device in a ~200 mT magnetic field show 10-fold increase in MB release compared to background release when the device is not actuated. 相似文献
945.
Geiger RA Chattopadhyay S Day VW Jackson TA 《Dalton transactions (Cambridge, England : 2003)》2011,40(8):1707-1715
Peroxomanganese(iii) adducts have been postulated as important intermediates in manganese-containing enzymes and small molecule oxidation catalysts. Synthetic peroxomanganese(iii) complexes are known to be nucleophilic and facilitate aldehyde deformylation, offering a convenient way to compare relative reactivities of complexes supported by different ligands. In this work, tetradentate dipyridyldiazacycloalkane ligands with systematically perturbed steric and electronic properties were used to generate a series of manganese(ii) and peroxomanganese(iii) complexes. X-Ray crystal structures of five manganese(ii) complexes all show the ligands bound to give trans complexes. Treatment of these Mn(II) precursors with H(2)O(2) and Et(3)N in MeCN at -40 °C results in the formation of peroxomanganese(iii) complexes that differ only in the identity of the pyridine ring substituent and/or the number of carbons in the diazacycloalkane backbone. To determine the effects of small ligand perturbations on the reactivity of the peroxo group, the more thermally stable peroxomanganese(iii) complexes were reacted with cyclohexanecarboxaldehyde. For these complexes, the rate of deformylation does not correlate with the expected nucleophilicity of the peroxomanganese(iii) unit, as the inclusion of methyl substituents on the pyridines affords slower deformylation rates. It is proposed that adding methyl-substituents to the pyridines, or increasing the number of carbons on the diazacycloalkane, sterically hinders nucleophilic attack of the peroxo ligand on the carbonyl carbon of the aldehyde. 相似文献
946.
Kinnings SL Liu N Tonge PJ Jackson RM Xie L Bourne PE 《Journal of chemical information and modeling》2011,51(2):408-419
Docking scoring functions are notoriously weak predictors of binding affinity. They typically assign a common set of weights to the individual energy terms that contribute to the overall energy score; however, these weights should be gene family dependent. In addition, they incorrectly assume that individual interactions contribute toward the total binding affinity in an additive manner. In reality, noncovalent interactions often depend on one another in a nonlinear manner. In this paper, we show how the use of support vector machines (SVMs), trained by associating sets of individual energy terms retrieved from molecular docking with the known binding affinity of each compound from high-throughput screening experiments, can be used to improve the correlation between known binding affinities and those predicted by the docking program eHiTS. We construct two prediction models: a regression model trained using IC(50) values from BindingDB, and a classification model trained using active and decoy compounds from the Directory of Useful Decoys (DUD). Moreover, to address the issue of overrepresentation of negative data in high-throughput screening data sets, we have designed a multiple-planar SVM training procedure for the classification model. The increased performance that both SVMs give when compared with the original eHiTS scoring function highlights the potential for using nonlinear methods when deriving overall energy scores from their individual components. We apply the above methodology to train a new scoring function for direct inhibitors of Mycobacterium tuberculosis (M.tb) InhA. By combining ligand binding site comparison with the new scoring function, we propose that phosphodiesterase inhibitors can potentially be repurposed to target M.tb InhA. Our methodology may be applied to other gene families for which target structures and activity data are available, as demonstrated in the work presented here. 相似文献
947.
Lee WH Wastney ME Jackson GS Martin BR Weaver CM 《Analytical and bioanalytical chemistry》2011,399(4):1613-1622
Calcium-41 (t(1/2) = 10(5) years) can be used after a single dose to follow calcium metabolism over a subject's lifetime. The aims of this study were to expand a (41)Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance for the design and interpretation of (41)Ca studies. Forty-two women >5 years post-menopause were given (41)Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ~5 years while subjects were free living. Urinary (41)Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (n = 13), studied previously in a 3-week balance and full kinetic study with (45)Ca, agreed with those using (41)Ca methodology. Thus, rates of bone resorption can be estimated from (41)Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation. 相似文献
948.
Peebles J Gwebu E Oyedeji O Nanyonga S Kunene N Jackson D Setzer W Oyedeji A 《Natural product communications》2011,6(12):1945-1948
Thelechitonia trilobata is regarded as a troublesome weed that grows to form a dense blanket over the soil preventing the growth of other crops in farmland. Although the plant is regarded as a notorious, invasive plant, its chemical composition and biological potential have not been reported. The essential oil was isolated from the fresh leaves of T. trilobata using hydrodistillation. alpha-Pinene (21.6%), alpha-phellendrene (21.0%), limonene (12.8%) and germacrene D (7.5%) were the major constituents of the oil. The essential oil was screened against agricultural pests. The anti-tick properties were tested on Ripicephalus e. ervertsi found on sheep, while repellency, fumigation, and contact toxicity tests were carried out with maize weevils. Except for the contact toxicity test, all other bioassays gave positive results. 相似文献
949.
Du J Yao S Seitz WR Bencivenga NE Massing JO Planalp RP Jackson RK Kennedy DP Burdette SC 《The Analyst》2011,136(23):5006-5011
The fluorescence emission of poly(N-isopropylacrylamide) (PNIPAM) covalently tagged with a 5-(dimethylamino)naphthalene-1-sulfonyl (dansyl) fluorophore and an iminodiacetic acid (IDA) chelator changes with temperature and with Cu(II) complexation. Increasing the temperature above the lower critical solution temperature (LCST) causes the polymer to collapse from a coil to a compact globule. This changes the environment experienced by the fluorophore causing a shift in maximum emission wavelength from 546 to 508 nm and an increase in the ratio of emission intensity at 508 nm to emission intensity at 546 nm from 0.70 to almost 1.40. Metal ions can be sensed by working at a temperature where the uncomplexed polymer is in an expanded state due to the charges on the ligand. Complexation with a metal ion such as Cu(II) neutralizes the charges on the ligand causing the polymer to collapse. At 35 °C, the emission intensity maximum shifted from 535 to 510 nm as Cu(II) concentration was increased and the intensity ratio increased from 0.84 to 1.28. By decoupling complexation from fluorescence, we have prepared a ratiometric fluorescent indicator for a metal ion that normally quenches fluorescence. The affinity for Cu(II) was found to be thermally tunable. The log apparent formation constants for the indicator-Cu(II) complex were estimated as the half way point in the intensity ratio vs. pCu curve. The values were determined to be 4.3 at 35 °C and 3.2 at 34 °C respectively. 相似文献
950.
The immiscible displacement in a capillary plane channel of a Newtonian liquid by a viscoplastic one that obeys a Papanastasiou’s
constitutive equation is numerically analyzed. An elliptic mesh generation technique, coupled with the Galerkin finite element
method is used to determine the velocity field and the configuration of the interface between the two materials. We investigate
the displacement efficiency and the flow patterns of the problem as functions of the dimensionless parameters that govern
the problem: the capillary number (Ca), the viscosity ratio of the two fluids (N
η
) and the yield number, (τ′0). The numerical results showed that for a fixed viscosity ratio, the fraction of mass attached to the wall is a decreasing
function of τ′0. We constructed maps of streamlines in the Cartesian space defined by τ′0 and Ca for fixed viscosity ratios in order to capture the rough location of bypass and recirculating flow regimes. Higher
yield number values induce bypass flow regimes, especially for high Ca. The dimensionless forms of the momentum conservation
equation and the force balance at the interface were essential for the understanding of the role played by the dimensionless
numbers that govern the problem. 相似文献