全文获取类型
收费全文 | 606篇 |
免费 | 34篇 |
国内免费 | 2篇 |
专业分类
化学 | 508篇 |
晶体学 | 5篇 |
力学 | 11篇 |
数学 | 43篇 |
物理学 | 75篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 10篇 |
2021年 | 21篇 |
2020年 | 17篇 |
2019年 | 19篇 |
2018年 | 10篇 |
2017年 | 16篇 |
2016年 | 32篇 |
2015年 | 13篇 |
2014年 | 21篇 |
2013年 | 32篇 |
2012年 | 48篇 |
2011年 | 62篇 |
2010年 | 38篇 |
2009年 | 30篇 |
2008年 | 55篇 |
2007年 | 34篇 |
2006年 | 29篇 |
2005年 | 27篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 15篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有642条查询结果,搜索用时 31 毫秒
51.
Danielle Vellucci Athit Kao Robyn M. Kaake Scott D. Rychnovsky Lan Huang 《Journal of the American Society for Mass Spectrometry》2010,21(8):1432-1445
Protein-protein interaction is one of the key regulatory mechanisms for controlling protein function in various cellular processes.
Chemical cross-linking coupled with mass spectrometry has proven to be a powerful method not only for mapping protein-protein
interactions of all natures, including weak and transient ones, but also for determining their interaction interfaces. One
critical challenge remaining in this approach is how to effectively isolate and identify cross-linked products from a complex
peptide mixture. In this work, we have developed a novel strategy using conjugation chemistry for selective enrichment of
cross-linked products. An azide-tagged cross-linker along with two biotinylated conjugation reagents were designed and synthesized.
Cross-linking of model peptides and cytochrome c as well as enrichment of the resulting cross-linked peptides has been assessed. Selective conjugation of azide-tagged cross-linked
peptides has been demonstrated using two strategies: copper catalyzed cycloaddition and Staudinger ligation. While both methods
are effective, Staudinger ligation is better suited for enriching the cross-linked peptides since there are fewer issues with
sample handling. LC MSn analysis coupled with database searching using the Protein Prospector software package allowed identification of 58 cytochrome
c cross-linked peptides after enrichment and affinity purification. The new enrichment strategy developed in this work provides
useful tools for facilitating identification of cross-linked peptides in a peptide mixture by MS, thus presenting a step forward
in future studies of protein-protein interactions of protein complexes by cross-linking and mass spectrometry. 相似文献
52.
Santos HM Glez-Peña D Reboiro-Jato M Fdez-Riverola F Diniz MS Lodeiro C Capelo-Martínez JL 《Electrophoresis》2010,31(20):3407-3419
In the present work we report on a novel and fast protocol for accurate bottom-up protein quantification that overcomes the drawbacks of in-gel digestion and MALDI analysis, while maintaining their benefits. It relies on the following steps: (i) gel electrophoresis separation of proteins, (ii) fast in-gel protein digestion with trypsin, (iii) (18)O-labeling through the decoupled method, (iv) quantification through selected peptides previously chosen using the (18)O inverse labeling approach and that, finally, (v) it takes advantage of software specifically developed to select the peptides that will drive the quantification of the protein in an automated mode. We have accurately quantified the following six proteins: glycogen phosphorylase, BSA, ovalbumin, carbonic anhydrase, trypsin inhibitor, and α-lactalbumin. As a case study we have quantified the protein vitellogenin in plasma of Cyprinus carpio exposed to high levels of estrogens. The proposed new protocol was validated against the traditional ELISA method; both were found to provide comparable results (non-parametric Mann-Whitney U-test). 相似文献
53.
Luu T Medos BJ Graham ER Vallee DM McDonald R Ferguson MJ Tykwinski RR 《The Journal of organic chemistry》2010,75(24):8498-8507
Terminal di-, tri-, tetra-, and pentaynes substituted with a variety of functional groups react with benzyl azide in the presence of CuSO(4)·5H(2)O and ascorbic acid to give derivatives of 4-ethynyl-, 4-butadiynyl-, 4-hexatriynyl-, and 4-octatetraynyl-1,2,3-triazoles in moderate to good yields. These reactions appear to proceed regioselectively, and functionalization occurs exclusively at the terminal alkyne moiety. As well, no evidence of multiple azide additions to the polyyne framework is observed. X-ray crystallographic analysis of nine derivatives is used to document the regioselectivity of the reaction as well as outline structural characteristics of the 1,2,3-triazole products. 相似文献
54.
Ji-Yao Li Biaoxin Chai Weizhen Zhang Xiaobin Wu Chao Zhang Danielle Fritze Zefeng Xia Cam Patterson Michael W Mulholland 《BMC neuroscience》2011,12(1):1-10
Background
Cigarette smoking enhances the risk of stroke. However, the underlying molecular mechanisms are largely unknown. The present study established an in vivo rat secondhand cigarette smoking (SHS) model and examined the hypothesis that SHS upregulates endothelin receptors with increased cerebrovascular contraction via the Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway.Results
Rats were exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was recorded by a sensitive myograph. The mRNA and protein expressions for endothelin receptors in cerebral arteries were studied by real-time PCR and Western blot. Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited stronger contractile responses (P < 0.05) mediated by endothelin type A (ETA) receptors. The expressions of mRNA and protein for ETA receptors in the cerebral arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not affect endothelin type B (ETB) receptor-mediated contractions, mRNA or protein levels. The results suggest that SHS upregulates ETA, but not ETB receptors in vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05). Raf-1 inhibitor, GW5074 suppressed the enhanced ETA receptor-mediated contraction, mRNA and protein levels induced by SHS. In addition, GW5074 inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf-1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway.Conclusions
SHS upregulates cerebrovascular ETA receptors via the Raf/ERK/MAPK pathway, which provides novel understanding of mechanisms involved in SHS-associated stroke. 相似文献55.
Huang J Wang AM Shetty A Maitz AH Yan D Doyle D Richey K Park S Pieper DR Chen PY Grills IS 《Magnetic resonance imaging》2011,29(7):993-1001
Objective
To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.Methods
Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.Results
Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.Conclusion
Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP. 相似文献56.
Naijue Zhu Danielle Lightsey Jiawang Liu Maryam Foroozesh Kathleen M. Morgan Edwin D. Stevens Cheryl L. Klein Stevens 《Journal of chemical crystallography》2010,40(4):343-352
Abstract
The single-crystal X-ray structures and in vivo activities of three aryl acetylenic inhibitors of cytochromes P450 1A1, 1A2, 2A6, and 2B1 have been determined and are reported herein. These are 1-ethynylpyrene, 1-propynylpyrene, and 4-propynylpyrene. To investigate electronic influences on the mechanism of enzyme inhibition, the experimental electron density distribution of 1-ethynylpyrene has been determined using low-temperature X-ray diffraction measurements, and the resulting net atomic charges compared with various theoretical calculations. A total of 82,390 reflections were measured with Mo Kα radiation to a (sinθ/λ)max = 0.985 Å−1. Averaging symmetry equivalent reflections yielded 8,889 unique reflections. A least squares refinement procedure was used in which multipole parameters were added to describe the distortions of the atomic electron distributions from spherical symmetry. A map of the model electron density distribution of 1-ethynylpyrene was obtained. Net atomic charges calculated from refined monopole population parameters yielded charges that showed that the terminal acetylenic carbon atom (C18) is more negative than the internal carbon (C17). Net atomic charges calculated by ab initio, density functional theory, and semi-empirical methods are consistent with this trend suggesting that the terminal acetylenic carbon atom is more likely to be the site of oxidation. This is consistent with the inhibition mechanism pathway that results in the formation of a reactive ketene intermediate. This is also consistent with assay results that determined that 1-ethynylpyrene acts as a mechanism-based inhibitor of P450s 1A1 and 1A2 and as a reversible inhibitor of P450 2B1. Crystallographic data: 1-ethynylpyrene, C18H10, P21/c, a = 14.571(2) Å, b = 3.9094(5) Å, c = 20.242(3) Å, β = 105.042(2)°, V = 1,113.5(2) Å3; 1-propynylpyrene, C19H12, P21/n, a = 8.970(2) Å, b = 10.136(1) Å, c = 14.080(3) Å, β = 99.77(2)°, V = 1,261.5(4) Å3; 4-propynylpyrene, C19H12, Pbca, a = 9.904(1) Å, b = 13.174(2) Å, c = 19.401(1) Å, V = 2,531.4(5) Å3. 相似文献57.
Vidoslav Dekić Niko Radulović Rastko Vukićević Biljana Dekić Danielle Skropeta Radosav Palić 《Magnetic resonance in chemistry : MRC》2010,48(11):896-902
Herein, we describe the synthesis and complete assignment of the 1H and 13C NMR chemical shifts of a series of antimicrobial 4‐arylamino‐3‐nitrocoumarin derivatives based on a combination of 1H and 13C NMR, 1H‐1H‐COSY, NOESY, HSQC and HMBC experiments. Conformational effects upon the chemical shifts of the coumarin moiety arising from the anisotropy of the aryl side group are briefly discussed. This study provides the first complete and fully assigned NMR data for this important group of antimicrobial compounds and bridges the gap existing in the literature with regard to NMR structural data for 4‐arylamino‐3‐nitrocoumarins. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
58.
J. L. C. Diniz R. D. Vieira J. T. Castro A. C. Benjamin J. L. F. Freire 《Experimental Mechanics》2006,46(6):765-775
This paper presents the analysis of stress and strain data acquired with the finite element method and with tests that used
post-yielding strain gages bonded onto the external surface of pipes that suffered thickness metal loss and that had been
loaded with internal pressure. These metal loss areas were produced by three different processes: actual internal corrosion,
careful machining of external patches by spark-erosion, and milling of internal or external patches to simulate limited or
extensive strip corrosion defects with depths up to 70% of the pipe’s thickness. Results show that: (1) the extensive longitudinal
internal or external defect areas behave as extensive strips with a high degree of freedom to deform elastically and plastically
in the circumferential and thickness directions, and (2) large restraints are offered to the longitudinal strains by the non-corroded
thick walls parallel to the strip. Using the above experimental observation, a simple mathematical model was developed to
predict the burst pressure of pipes with longitudinal extensive and reasonably constant depths of metal loss. This model employed
thin-pipe-strength-of-material equations associated to a bulging correction factor, the material’s uniaxial ultimate strength
and the von Mises criterion. The onset of plastic collapse predicted by the simple model was successfully compared with results
determined from actual hydrostatic tests that were carried out with full scale pipe specimens and from finite element results
generated by the use of a commercial program. The developed model was also helpful in showing that the yield and burst behaviors
of new or corroded pipeline specimens under laboratory test conditions can be directly compared and extended to the yield
and burst behaviors of buried pipeline in field operation. 相似文献
59.
High Sensitive Microsensor Based on Organic‐Inorganic Composite for Two‐Dimensional Mapping of H2O2 by SECM 下载免费PDF全文
Danielle Diniz Justino Isabel Lourenço Torres Rita de Cássia Silva Luz Flavio Santos Damos 《Electroanalysis》2015,27(5):1202-1209
The present work describes the development of a selective, sensitive and stable sensing microsensor for scanning electrochemical microscopy (SECM) to measure H2O2 during electrochemical reduction of oxygen. The microsensor is based on graphene and Poly(3,4‐ethylenedioxythiophene) composite as support to iron (III) hexacyanoferrate (II) (PEDOT/graphene/FeIII4[FeII(CN)6]3 microsensor). The electrochemical properties of the PEDOT/graphene/FeIII4[FeII(CN)6]3 microsensor were investigated by cyclic voltammetry (CV) and scanning electrochemical microscopy (SECM). The PEDOT/graphene/FeIII4[FeII(CN)6]3 microsensor showed an excellent electrocatalytic activity toward hydrogen peroxide (H2O2) reduction with a diminution of the overpotential of about 500 mV in comparison to the process at a bare gold microelectrode. The microsensor presented excellent performance for two dimensional mapping of H2O2 by SECM in 0.1 mol L?1 phosphate buffer solution (pH 7.0). Under optimized conditions, a linear response range from 1 up to 1000 µmol L?1 was obtained with a sensitivity of 0.08 nA L µmol?1 and limit of detection of 0.5 µmol L?1. 相似文献