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41.
42.
Development and validation of a RP‐HPLC method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study
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Vijay Kumar S Vinay Dhiman Kalpesh Kumar Giri Kuldeep Sharma Mohd Zainuddin Ramesh Mullangi 《Biomedical chromatography : BMC》2015,29(9):1325-1329
A novel, simple, specific, sensitive and reproducible high‐performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of tofacitinib in rat plasma. The bioanalytical procedure involves extraction of tofacitinib and itraconazole (internal standard, IS) from rat plasma with a simple liquid–liquid extraction process. The chromatographic analysis was performed on a Waters Alliance system using a gradient mobile phase conditions at a flow rate of 1.0 mL/min and C18 column maintained at 40 ± 1 °C. The eluate was monitored using an UV detector set at 287 nm. Tofacitinib and IS eluted at 6.5 and 8.3 min, respectively and the total run time was 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 182–5035 ng/mL (r2 = 0.995). The intra‐ and inter‐day precisions were in the range of 1.41–11.2 and 3.66–8.81%, respectively, in rat plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
43.
Quantitation of VEGFR2 (vascular endothelial growth factor receptor) inhibitors – review of assay methodologies and perspectives
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Kuldeep Sharma P. S. Suresh Ramesh Mullangi N. R. Srinivas 《Biomedical chromatography : BMC》2015,29(6):803-834
The introduction of small‐molecule tyrosine kinase VEGFR2 (vascular endothelial growth factor receptor) inhibitors has added another dimension in the treatment of several oncology indications as they offer a unique mechanism. The VEGFR2 inhibitors have demonstrated superior benefits in treating certain types of cancer, such as renal cell carcinoma and hepatocellular carcinoma, as a monotherapy option. Many of the approved VEGFR2 inhibitors have also shown promise when used in combination with other anticancer agents. There are numerous bioanalytical methods published for the analysis of VEGFR2 inhibitors in preclinical and clinical samples. This review covers VEGFR2 inhibitors such as sunitinib, sorafenib, pazopanib and JI‐101. In addition to providing a comprehensive review of the available methods for the above‐mentioned VRGFR2 inhibitors, it also provides information on assays that can simultaneously measure multiple tyrosine kinase inhibitors, including VEGFR2 molecules. Based on the review, the published methodologies using LC/MS‐MS or HPLC‐UV are adequate for the quantification of the VEGFR2 inhibitors and can easily be established in a modern day bioanalytical laboratory. The availability of a plethora of assays for multiple tyrosine kinase inhibitors makes it easy to analyze a panel of compounds to support either therapeutic drug monitoring and/or clinical pharmacokinetics. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
44.
Rajesh S. Bhosale Chandrakant V. Magar Kuldeep S. Solanke Sandeep B. Mane Sunil S. Choudhary 《合成通讯》2013,43(24):4353-4357
An iodine/DMSO system is introduced as an excellent catalyst in three‐component coupling reactions of tetrahydrobenzo[b]pyran synthesis. The reaction proceeds quickly under very mild reaction conditions. 相似文献
45.
The electro-optical and dielectric responses of the fullerenes C60-doped ferroelectric liquid crystal (FLC) nanocolloids are reported. Order parameter and phase transition temperature remain invariant as a function of varying dopant concentration (0.10 wt% to 0.50 wt%). Faster switching response of nanocolloids comparing to that of the non-doped FLC is manifested by increase in the localised electric field (around 76% increment for 0.50 wt%), while reduction in the spontaneous polarisation could be the result of anti-parallel correlation amid dopant and FLC dipoles. Decrease in dielectric constant, absorption strength, dielectric strength and rotational viscosity of FLC nanocolloids than that of non-doped FLC is the other consequence of C60 doping. Goldstone-mode relaxation frequency is found to be increased with increasing doping concentration of C60 in FLC. 相似文献
46.
A. Kumar G. K. Singh B. Kuldeep 《Journal of Mathematical Modelling and Algorithms》2011,10(3):213-226
An improved and simplified approach is presented for design of nearly perfect reconstructed cosine-modulated (CM) filter banks
with prescribed stopband attenuation and channel overlapping. The method employs Kaiser window technique to design the prototype
filter for filter banks with the novelty of exploiting spline functions in the transition band of the ideal filter instead
of using the conventional brick-wall filter based on linear optimization of filter coefficients such that their value at frequency
(ω = π/2M) is 0.707. The simulation results illustrate the proposed method and its improvement over other existing methods in terms
of amplitude distortion (e
am
), number of iterations (NOI), aliasing distortion (e
a
) and computation time (CPU time). 相似文献
47.
Faisal Omar Abu Montakim Tareq Ali M. Alqahtani Kuldeep Dhama Mohammed Abu Sayeed Talha Bin Emran Jesus Simal-Gandara 《Molecules (Basel, Switzerland)》2021,26(8)
Plant-based indole alkaloids are very rich in pharmacological activities, and the indole nucleus is considered to contribute greatly to these activities. This review’s fundamental objective is to summarize the pharmacological potential of indole alkaloids that have been derived from plants and provide a detailed evaluation of their established pharmacological activities, which may contribute to identifying new lead compounds. The study was performed by searching various scientific databases, including Springer, Elsevier, ACS Publications, Taylor and Francis, Thieme, Wiley Online Library, ProQuest, MDPI, and online scientific books. A total of 100 indole compounds were identified and reviewed. The most active compounds possessed a variety of pharmacological activities, including anticancer, antibacterial, antiviral, antimalarial, antifungal, anti-inflammatory, antidepressant, analgesic, hypotensive, anticholinesterase, antiplatelet, antidiarrheal, spasmolytic, antileishmanial, lipid-lowering, antimycobacterial, and antidiabetic activities. Although some compounds have potent activity, some only have mild-to-moderate activity. The pharmacokinetic profiles of some of the identified compounds, such as brucine, mitragynine, 7-hydroxymitragynine, vindoline, and harmane, were also reviewed. Most of these compounds showed promising pharmacological activity. An in-depth pharmacological evaluation of these compounds should be performed to determine whether any of these indoles may serve as new leads. 相似文献
48.
A new fluorescent probe based on a bis-benzimidazole diamide N 2,N 2′-bis[(1-ethyl-benzimidazol-2-yl)methyl]biphenyl-2,2′-dicarboxamide ligand L 1 with a biphenyl spacer group and a Copper(II) trinuclear metallacycle has been synthesized and characterized by X-ray single crystallography, elemental and spectral (FT-IR, 1H & 13C NMR, UV-Visible) analysis. The fluorescence spectra of L 1 in MeOH show an emission band centered at 300 nm. This band arises due to benzimidazolyl moiety in the ligating system. The diamide L 1 in the presence of Cu2+ show the simultaneous ‘quenching’ of (300 nm) and ‘enhancement’ of (375 nm) emission band. Similar fluorescence behavior was found in water–methanol mixture (9:1). The new emission band at 375 nm is attributed to intra ligand π–π* transition of the biphenyl moiety. L 1 exhibited high selectivity and sensitivity towards Cu2+ in both the medium over other common metal ions like Ni2+, Co2+, Mn2+, Mg2+, Zn2+, Pb2+ and Hg2+. The binding constant with Cu2+ was calculated by the Benesi-Hildebrand equation. Selective “off-on-off” behavior of L 1 in methanol has also been studied. The fluorescent intensity of 375 nm bands in L 1 enhances (turns-on) upon addition of Cu2+ and quenches (turn-off) upon addition of Na2-EDTA. 相似文献
49.
The β(3)-adrenegic receptor (β(3)-AR) selectivity over β(1)- and β(2)-ARs has been the most important aspect for successful therapeutic agents for obesity and type-II diabetes, as the concomitant activation of β(1)- and β(2)-ARs would lead to undesirable side effects, such as increased heart rate. In order to explore the structural basis for the β-AR subtype selectivity of agonists and anatagonists, a three-dimensional structure of until date unresolved β(3)-AR has been modeled, compared with the resolved X-ray structures of β(1)- and β(2)-ARs, and used to study its stereoselective binding with until-date known diverse classes of representative agonists and antagonist. The obtained binding structures and calculated prime molecular mechanics-generalized Born surface area (MM-GBSA) binding free energies consistently reveal that while the subtype selectivity is strongly governed by the residues present in the extracellular ends of TM3, TM5, TM6, TM7 helices and of the ECL2 domain, the binding affinity is governed by the conserved residues present in the deep pocket limiting the degree of conformational and rotational freedoms to the bound ligand. The study demonstrates that the key structural requirements for the β(3)-selectivity are: (i) a negatively ionizable group (NIG) for direct interaction with β(3)-specific residue R315(6.58), (ii) a linker (9-10 ? length) between the protonated amine and NIG, and (iii) a substituted aryl ring directly attached to the β-hydroxyl carbon. The new computational insights acquired in this study are expected to be valuable in structure-based rational design of high-affinity agonists and antagonists with pronounced β(3)-selectivity for successful therapeutic agents for type-II diabetes and obesity. 相似文献
50.
Sambasivarao Kotha Deepti Bansal Kuldeep Singh Subhasree Banerjee 《Journal of organometallic chemistry》2011,696(9):1856-421
A simple methodology to a unique macrocyclic α-amino acid (AAA) derivative involving three step synthetic sequence has been reported. In addition, various ruthenium based catalysts were studied to enhance the selectivity of the desired macrocyclic AAA derivative 6. The fluorescence behavior of these AAA derivatives 5 and 6 indicate their potential applications in biological sciences as biomarkers, ion sensors and peptidomimetics. 相似文献