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71.
Mendoza R Petros AM Liu Y Thimmapaya R Surowy CS Leise WF Pereda-Lopez A Panchal SC Sun C 《Bioorganic & medicinal chemistry letters》2011,21(18):5248-5250
NMR-based screening of protein targets has become a well established part of the drug discovery process especially with respect to fragments. However, as target size increases the two-dimensional spectra typically used for such screening become more crowded due to the increased number of signals, and the individual signals broaden due to the decreased rotational correlation time of the protein. Here we present an NMR-based functional assay for the branched-chain aminotransferase BCATc, a dimer with a total molecular weight of 88 kDa, which overcomes the limitations of the typical protein-based NMR screening method. BCATc is involved in glutamate production in the brain and is a therapeutic target for neuronal disorders involving a glutamatergic mechanism. Several fragments which inhibit BCATc were discovered using this assay and these may serve as novel cores for the development of potent BCATc inhibitors. 相似文献
72.
Reshma Perween Shubbir Ahmed Tripti Shrivastava Hilal A. Parray Balwant Singh Kamal S. Pindari Chandresh Sharma Shivangi Shukla Subrata Sinha Anil Kumar Panchal Rajesh Kumar 《Biotechnology progress》2021,37(3):e3136
Phage display antibody (PDA) libraries, allows the rapid isolation and characterization of high specificity monoclonal antibodies for therapeutic and diagnostic applications. However, selection of positive binding clones from synthetic and semi-synthetic libraries has an inherent bias towards clones containing randomly generated amber stop codons, complicating the identification of high affinity binding antibodies. We screened Tomlinson I and J library against receptor binding domain (RBD) of SARS CoV2, eight clones which showed positive binding in phage ELISA, contained one or more amber stop codons in their single-chain antibody fragment (scFv) gene sequences. The presence of amber stop codons within the antibody sequence causes the premature termination of soluble form of scFv expression in nonsuppressor Escherichia coli strain. In the present study, we have used a novel strategy that allows soluble expression of scFvs having amber stop codon in their gene sequences (without phage PIII protein fusion), in the suppressor strain. This strategy of introduction of Ochre (TAA) codon at the junction of scFv and PIII gene, speeds up the initial screening process which is critical for selecting the right scFvs for further studies. Present strategy leads to the identification of a scFv, B8 that binds specifically with nanomolar affinity toward SARS CoV 2 RBD, which otherwise lost in terms of traditional methodology. 相似文献
73.
A switch‐off fluorescence probe towards Pb(II) and cu(II) ions based on a calix[4]pyrrole bearing amino‐quinoline group 下载免费PDF全文
A new fluorescence receptor calix[4]pyrrole‐N‐(quinoline‐8‐yl) acetamide (CAMQ) containing a pyrrolic ring connected via the meso‐position was synthesized, purified and characterized by elemental analysis, NMR and mass spectroscopy. This compound was examined for its fluorescence properties towards different metal ions e.g. Ag(I), Hg(II), Co(II), Ca(II), Ni(II), Zn(II), Cr(II), Ba(II), Fe(II), Cu(II), Pb(II)and Mg(II) ions by spectrophotometry and spectrofluorometry. It was concluded that the compound (CAMQ) possessed significantly enhanced selectivity for Pb(II) and Cu(II) ions in dimethyl sulfoxide (DMSO) even at very low concentrations (1 μM). It exhibit ‘turn‐on’ fluorescence when exposed to Pb(II) and Cu(II) and did so in preference to other metal ions. The binding constants, stoichiometry and quantum yields have been determined. The quenching mechanism was assessed using the Stern–Volmer equation and was also discussed. 相似文献
74.
A standard protocol for isolation of buffalo prolactin (buPRL) was modified at the alcohol precipitation step. This modification could separate lower molecular weight prolactin from the higher molecular weight prolactin (PRL). Reloading the prolactin onto a Sephacryl S-200 gel purified the buPRL monomer. The purity of buPRL monomer was confirmed by 15% SDS PAGE. The buPRL monomer was >90% pure. It was characterized by specific anti-buPRL serum in ELISA and Western blot. A native PAGE of the PRL showed three charge isoforms. A protocol was standardized to separate prolactin monomeric least acidic isoforms using an anion exchanger. 相似文献
75.
Nablo BJ Halverson KM Robertson JW Nguyen TL Panchal RG Gussio R Bavari S Krasilnikov OV Kasianowicz JJ 《Biophysical journal》2008,95(3):1157-1164
Nonelectrolyte polymers of poly(ethylene glycol) (PEG) were used to estimate the diameter of the ion channel formed by the Bacillus anthracis protective antigen 63 (PA63). Based on the ability of different molecular weight PEGs to partition into the pore and reduce channel conductance, the pore appears to be narrower than the one formed by Staphylococcus aureus α-hemolysin. Numerical integration of the PEG sample mass spectra and the channel conductance data were used to refine the estimate of the pore's PEG molecular mass cutoff (∼1400 g/mol). The results suggest that the limiting diameter of the PA63 pore is <2 nm, which is consistent with an all-atom model of the PA63 channel and previous experiments using large ions. 相似文献
76.
Padrick SB Cheng HC Ismail AM Panchal SC Doolittle LK Kim S Skehan BM Umetani J Brautigam CA Leong JM Rosen MK 《Molecular cell》2008,32(3):426-438
Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses. 相似文献
77.
On the validity of nested clade phylogeographical analysis 总被引:2,自引:1,他引:1
78.
J Panchal H Amirsheybani R Gurwitch V Cook P Francel B Neas N Levine 《Plastic and reconstructive surgery》2001,108(6):1492-8; discussion 1499-500
The objective of this study was to determine whether children with nonsyndromic craniosynostosis and plagiocephaly without synostosis demonstrated cognitive and psychomotor delays when compared with a standardized population sample. This was the initial assessment of a larger prospective study, which involved 21 subjects with nonsyndromic craniosynostosis (mean age, 10.9 months) and 42 subjects with plagiocephaly without synostosis (mean age, 8.4 months). Each child was assessed using the Bayley Scales of Infant Development-II (BSID-II) for cognitive and psychomotor development before therapeutic intervention (surgery for craniosynostosis and molding-helmet therapy for plagiocephaly without synostosis). The distribution of the scores was divided into four groups: accelerated, normal, mild delay, and significant delay. The distributions of the mental developmental index (MDI) and the psychomotor developmental index (PDI) were then compared with a standardized Bayley's age-matched population, using Fisher's exact chi-square test. Within the craniosynostosis group, the PDI scores were significantly different from the standardized distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the craniosynostosis group were accelerated, 43 percent were normal, 48 percent had mild delay, and 9 percent had significant delay. In contrast, the MDI scores were not statistically different (p = 0.08). Within the group with plagiocephaly without synostosis, both the PDI and MDI scores were significantly different from the normal curve distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the group with plagiocephaly without synostosis were accelerated, 67 percent were normal, 20 percent had mild delay, and 13 percent had significant delay. With regard to the MDI scores, 0 percent of the subjects in this group were accelerated, 83 percent were normal, 8 percent had mild delay and 9 percent had significant delay. This study indicates that before any intervention, subjects with single-suture syndromic craniosynostosis and plagiocephaly without synostosis demonstrate delays in cognitive and psychomotor development. Continued postintervention assessments are needed to determine whether these developmental delays can be ameliorated with treatment. 相似文献
79.
Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure 总被引:4,自引:0,他引:4
Kennedy Sarah L.; Stanley William C.; Panchal Ashish R.; Mazzeo Robert S. 《Journal of applied physiology》2001,90(1):17-22
The purpose of this study was toexamine the effect of acute (24 h) and chronic (5 wk) hypobaric hypoxicexposure equivalent to a simulated altitude of 4,300 m (446 mmHg) onthe enzymes of fat metabolism. Heart, liver, and skeletal muscle weretaken from 32 male Sprague-Dawley rats. Altitude exposure did notaffect the activity of citrate synthase in any of the tissues,suggesting that mitochondrial content was unchanged. Carnitinepalmitoyltransferase-I (CPT-I) activity was significantly reduced inthe heart by both acute and chronic high altitude exposure comparedwith controls. A similar reduction was found for CPT-I activity inextensor digitorum longus after acute and chronic exposurecompared with control animals. CPT-I activity was not affected byaltitude exposure in the soleus muscle or the liver. 3-Hydroxyacyl-CoAdehydrogenase (-HAD) activity was significantly depressed in thehearts of chronically exposed animals compared with controls. Nodifference between acute and control animals was found in the heart for-HAD activity. Liver -HAD activity was also significantlydecreased in the acclimatized as well as in the acute animals comparedwith the control group. Quadriceps -HAD activity was reduced for the chronic animals only compared with controls. These data suggest thatacclimatization to high altitude selectively decreases key enzymes infat utilization and oxidation in the heart, liver, and select skeletal muscles. 相似文献
80.
Two triple resonance experiments, HNN and HN(C)N, are presented which correlate HN and 15N resonances sequentially along the polypeptide chain of a doubly (13C, 15N) labeled protein. These incorporate several improvements over the previously published sequences for a similar purpose and have several novel features. The spectral characteristics enable direct identification of certain triplets of residues, which provide many starting points for the sequential assignment procedure. The experiments are sensitive and their utility has been demonstrated with a 22 kDa protein under unfolding conditions where most of the standard triple resonance experiments such as HNCA, CBCANH etc. have limited success because of poor amide, C and C chemical shift dispersions. 相似文献