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51.
In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle.  相似文献   
52.
Correction for ‘Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery’ by Christine N. Morrison et al., Chem. Sci., 2020, 11, 1216–1225, https://doi.org/10.1039/C9SC05586J.

The authors regret that in the original article, inhibitory values reported for some metallofragments were incorrect. Unfortunately, DMSO stock solutions of reportedly active ferrocene-based metallofragments were found to decompose in the presence of light, which resulted in inaccurate inhibition values. The authors maintain that the core conclusions of the paper are accurate and the utility of three-dimensional metal complexes for fragment-based drug discovery has merit.In the original article, ‘class A’ metallofragments are comprised of ferrocene derivatives (Fig. 1). Some of these ferrocene fragments (specifically those containing carbonyl groups) are reported as broadly inhibiting several protein targets. It was noted in our original report that the ferrocene scaffold was likely promiscuous due to its lipophilicity and potential redox activity, but that it might still serve as a useful metallofragment for fragment-based drug discovery (FBDD) campaigns. However, re-evaluation of these compounds against the influenza endonuclease (PAN) failed to reproduce our original inhibition results for the class A metallofragments using freshly prepared stocks, indicating a problem with the materials used in the original study.Open in a separate windowFig. 1Chemical structures of class A metallofragments.Several compounds from class A were originally reported as having near complete (100%) inhibition against PAN endonuclease at an inhibitor concentration of 200 μM (and2).2). However, when re-evaluated under identical conditions, using freshly prepared DMSO stock solutions, inhibition was only observed with one fragment of this class (A22, Fig. 1), with the previously reported highly active fragments (A4, A7–A21,
CompoundA1A2A3A4A5A7A8A9A10A11
Reported12 ± 6<1<145 ± 148 ± 7103 ± 5103 ± 453 ± 546 ± 790 ± 5
Corrected3 ± 10n.d.18 ± 36 ± 321 ± 59 ± 310 ± 54 ± 216 ± 410 ± 7
Open in a separate windowan.d. = not determined.
CompoundA12A14A15A16A17A18A19A20A21A22
Reported66 ± 526 ± 655 ± 719 ± 8100 ± 4107 ± 632 ± 880 ± 410 ± 1688 ± 9
Corrected9 ± 410 ± 518 ± 115 ± 65 ± 3<111 ± 9<1< 193 ± 1
Open in a separate windowReported and re-evaluated percent inhibition values of representative metallofragments against PAN endonuclease at 200 μM inhibitor concentration. Each compound was tested in triplicate from either two or three independent experimentsa
CompoundA1B1C1D1E1F1G1
Reported12 ± 64 ± 670 ± 2320 ± 1118 ± 982 ± 516 ± 6
Re-evaluated<519 ± 875 ± 1114 ± 9<510 ± 14<5
Open in a separate windowan.d. = not determined.
CompoundH1I1J1K1L1M1DPBA
Reported31 ± 626 ± 725 ± 699 ± 312 ± 426 ± 4n.d.
Re-evaluated25 ± 9<541 ± 683 ± 330 ± 854 ± 597 ± 1
Open in a separate windowIn the original article, one representative member of each metallofragment class was assessed for stability by NMR. Compound A1 (ferrocene) proved stable in DMSO and class A metallofragments were stored as DMSO stocks at −80 °C, but were not consistently protected from light. As noted above, many of the derivatives in class A contain a ferrocenyl carbonyl motif. It has been previously reported that ferrocenyl ketones can undergo photoaquation (λ > 280 nm) in wet DMSO to produce a monocyclopentadienyliron cation, the anionic ligand, and free cyclopentadiene.1 Suspecting issues with photostability, we dissolved several of the ferrocenyl fragments in DMSO-d6, exposed them to ambient room light (fluorescent light bulb), and monitored stability by NMR. Indeed, photoinstability was confirmed by the observance of free cyclopentadienyl peaks appearing in the 1H NMR spectrum (Fig. 2). It should also be noted that while the fresh stock of A22 retained significant inhibition against PAN, it also exhibits sensitivity to light in DMSO.Open in a separate windowFig. 2Compound A7 in DMSO-d6 (left) and after exposure to ambient light for 24 h (right) demonstrating the photoinstability of this compound.Based on these findings, the authors regret that the inhibitory data associated with class A metallofragments are incorrect, likely because of photodecomposition of these ferrocene derivatives. To confirm if other classes of metallofragments were correctly reported, a representative member of each class was evaluated against PAN endonuclease at an inhibitor concentration of 200 μM using freshly prepared DMSO stocks. Each compound was tested in triplicate in two or three independent experiments, with the addition of 2,4-dioxo-4-phenylbutanoic acid (DPBA) as a positive control.2 Fortunately, these experiments largely reproduced our original findings. Although several fragments showed slightly greater activity upon re-evaluation (J1, L1, M1, Fig. 3), only one fragment initially identified as a hit (>50% inhibition) failed to show activity when re-examined (F1, Fig. 3). Other than compound F1, all selected compounds designated as ‘hits’ (>50% inhibition) retained a high level of inhibitory activity upon re-evaluation. Taken together, the authors believe the inaccuracies stemming from photostability issues are limited to class A compounds; however, these inaccuracies would include all other inhibition data reported for class A compounds, including assay data against other enzyme targets, IC50 values, and thermal shift assay (TSA) binding data. Furthermore, the hit rate against each target is likely lower than reported, with PAN having an adjusted hit rate of ∼28% (20/71).Open in a separate windowFig. 3Chemical structures of representative metallofragments from each class re-examined for inhibition activity against PAN endonuclease.The authors maintain that three-dimensional metallofragments represent a useful new line of inquiry for FBDD and our ongoing studies seek to further test this hypothesis. The core message of our original study – the ability of metallofragments to be useful scaffolds for FBDD that occupy hard-to-access three-dimensional chemical space – remains unchanged. However, as demonstrated by our error, the authors acknowledge that metallofragments may pose unique challenges that must be carefully considered and controlled for when using them in FBDD campaigns.The authors would like to take this opportunity to thank the readers who alerted them to the concerns regarding the inhibitory activities and allowed them to reinvestigate. Both the authors and the Royal Society of Chemistry appreciate their support.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.  相似文献   
53.
Sets with B-action and linear algebra     
T. Stokes 《Algebra Universalis》1998,39(1-2):31-43
Let B be a Boolean ring. Any unital B-module M has a B-action given by for all . We show that any set with B-action may be represented as a subset with B-action of a unital B-module. We extend this to algebras with B-action and apply it to if-then-else algebras over Boolean algebras by viewing them as semilattices with B-action. Received May 23, 1996; accepted in final form February 4, 1998.  相似文献   
54.
Interface dynamics in porous media: A random-field description     
Stokes JP  Kushnick AP  Robbins MO 《Physical review letters》1988,60(14):1386-1389
  相似文献   
55.
Rapid Quantification of 25-Hydroxyvitamin D<Subscript>3</Subscript> in Human Serum by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry     
Yulin Qi  Miriam Müller  Caroline S. Stokes  Dietrich A. Volmer 《Journal of the American Society for Mass Spectrometry》2018,29(7):1456-1462
LC-MS/MS is widely utilized today for quantification of vitamin D in biological fluids. Mass spectrometric assays for vitamin D require very careful method optimization for precise and interference-free, accurate analyses however. Here, we explore chemical derivatization and matrix-assisted laser desorption/ionization (MALDI) as a rapid alternative for quantitative measurement of 25-hydroxyvitamin D3 in human serum, and compare it to results from LC-MS/MS. The method implemented an automated imaging step of each MALDI spot, to locate areas of high intensity, avoid sweet spot phenomena, and thus improve precision. There was no statistically significant difference in vitamin D quantification between the MALDI-MS/MS and LC-MS/MS: mean ± standard deviation for MALDI-MS—29.4?±?10.3 ng/mL—versus LC-MS/MS—30.3?±?11.2 ng/mL (P?=?0.128)—for the sum of the 25-hydroxyvitamin D epimers. The MALDI-based assay avoided time-consuming chromatographic separation steps and was thus much faster than the LC-MS/MS assay. It also consumed less sample, required no organic solvents, and was readily automated. In this proof-of-concept study, MALDI-MS readily demonstrated its potential for mass spectrometric quantification of vitamin D compounds in biological fluids.
Graphical Abstract ?
  相似文献   
56.
Demonstration of an integrated capillary electrophoresis-laser-induced fluorescence fiber-optic sensor     
Sepaniak MJ  Vo-Dinh T  Stokes DL  Tropina V  Dickens JE 《Talanta》1996,43(11):1889-1901
A unique integrated separation-based fiber-optic sensor for remote analysis, that incorporates capillary electrophoresis (CE) directly at the fiber sensing terminus is described for the first time. Based on laser-induced fluorescence detection, the sensor offers the potential for high sensitivity. Although the broad-band nature of fluorescence spectra limits selectivity, the high separation power of CE provides a unique dimension of selectivity, while permitting a design of diminutive size. Previously reported fluorescence-based sensors that utilize a chemical reagent phase to impart selectivity tend to be inflexible (not readily adaptable to the detection of different species) and "one-measurement-only" sensors. Conversely, the CE-based fiber-optic sensor described here is both versatile and reusable. The analysis speed and the potential for remote control are further attributes which make the system amenable to remote sensing. A "single-fiber" optical detection arrangement and a "single-reservoir" CE system with the fiber-optic probing the outlet of the separation capillary are employed. A preliminary evaluation of the separation characteristics of this CE-based sensor is presented. Highlights include an observed separation efficiency of up to 3000 theoretical plates (8 cm separation capillary) and migration time reproducibility of less than 10% for frontal mode CE separations. The potential utility of the sensor for remote analysis is demonstrated with separations involving the CE analysis of charged fluorescent dyes, CE analysis of metal complexes based on in situ complexation and micellar electrokinetic capillary chromatographic analysis of neutral fluorescent compounds.  相似文献   
57.
Broadband Noise in Orthorhombic TaS3     
O Nark. Rorbins  J. P. Stokes  S. Bhattacharya  R. A. Klemm 《Molecular Crystals and Liquid Crystals》2013,570(1-4):63-66
We report experimental results on the broadband noise in sliding charge density wave conductor orthorhombic TaSn. The experimental results are in excellent agreement with a phenomenological model based on fluctuations in threshold field due to deformations of the sliding condensate.  相似文献   
58.
How to generalise demonic composition     
Stokes  Tim 《Semigroup Forum》2021,102(1):288-314
Semigroup Forum - Demonic composition is defined on the set of binary relations over the non-empty set X, $$Rel_X$$ , and is a variant of standard or “angelic” composition. It arises...  相似文献   
59.
Übergangsmetallkatalysierte C‐C‐Kupplungen mit Ethylen im Labormaßstab     
Vaneet Saini  Benjamin J. Stokes  Matthew S. Sigman 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2013,125(43):11414-11429
  相似文献   
60.
The Casimir effect for fields with arbitrary spin     
Adam Stokes  Robert Bennett 《Annals of Physics》2015
The Casimir force arises when a quantum field is confined between objects that apply boundary conditions to it. In a recent paper we used the two-spinor calculus to derive boundary conditions applicable to fields with arbitrary spin in the presence of perfectly reflecting surfaces. Here we use these general boundary conditions to investigate the Casimir force between two parallel perfectly reflecting plates for fields up to spin-2. We use the two-spinor calculus formalism to present a unified calculation of well-known results for spin-1/2 (Dirac) and spin-1 (Maxwell) fields. We then use our unified framework to derive new results for the spin-3/2 and spin-2 fields, which turn out to be the same as those for spin-1/2 and spin-1. This is part of a broader conclusion that there are only two different Casimir forces for perfectly reflecting plates—one associated with fermions and the other with bosons.  相似文献   
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