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41.
Catimel B; Scott AM; Lee FT; Hanai N; Ritter G; Welt S; Old LJ; Burgess AW; Nice EC 《Glycobiology》1998,8(9):927-938
We describe a novel immobilization technique to investigate interactions
between immobilized gangliosides (GD3, GM1, and GM2) and their respective
antibodies, antibody fragments, or binding partners using an optical
biosensor. Immobilization was performed by direct injection onto a
carboxymethyldextran sensor chip and did not require derivatization of the
sensor surface or the ganglioside. The ganglioside appeared to bind to the
sensor surface by hydrophobic interaction, leaving the carbohydrate epitope
available for antibody or, in the case of GM1, cholera toxin binding. The
carboxyl group of the dextran chains on the sensor surface did not appear
to be involved in the immobilization as evidenced by equivalent levels of
immobilization following conversion of the carboxyl groups into acyl amino
esters, but rather the dextran layer provided a hydrophilic coverage of the
sensor chip which was essential to prevent nonspecific binding. This
technique gave better reactivity and specificity for anti- ganglioside
monoclonal antibodies (anti-GD3: KM871, KM641, R24; and anti-GM2: KM966)
than immobilization by hydrophobic interaction onto a gold sensor surface
or photoactivated cross-linking onto carboxymethydextran. This rapid
immobilization procedure has facilitated detailed kinetic analysis of
ganglioside/antibody interactions, with the surface remaining viable for a
large number of cycles (>125). Kinetic constants were determined from
the biosensor data using linear regression, nonlinear least squares and
equilibrium analysis. The values of kd, ka, and KAobtained by nonlinear
analysis (KAKM871 = 1.05, KM641 = 1.66, R24 = 0.14, and KM966 = 0.65 x
10(7) M- 1) were essentially independent of concentration and showed good
agreement with data obtained by other analytical methods.
相似文献
42.
Shawn G. Payne David N. Brindley Larry J. Guilbert 《Journal of cellular physiology》1999,180(2):263-270
The activation of sphingomyelinase and the subsequent generation of ceramide are emerging as important components of signaling pathways leading to apoptosis. The combination of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) induces apoptosis of primary placental trophoblasts in vitro. This apoptosis is inhibited completely by cotreatment with epidermal growth factor (EGF). We therefore examined the role of sphingomyelinase and ceramide in trophoblast apoptosis and how this may be influenced by EGF. Exogenous C16-ceramide (20 μM) and acid sphingomyelinase induced trophoblast apoptosis, an effect abrogated completely by cotreatment with 10 ng/ml EGF. Neutral sphingomyelinase also increased ceramide levels but did not induce apoptosis. Treatment with EGF alone decreased cellular ceramide levels. This decrease could be blocked by cotreatment with the acid ceramidase inhibitor N-oleoylethanolamine (OE). OE alone increased ceramide levels and induced apoptosis that could not be blocked by cotreatment with EGF. In contrast, the alkaline ceramidase inhibitor D-MAPP, although it also increased ceramide levels, did not induce apoptosis nor did it affect TNF-α/IFN-α-induced cell death. These results implicate sphingolipids as important mediators in trophoblast apoptosis and suggest that the antiapoptotic properties of EGF can in part be explained by its control of ceramide concentrations in trophoblasts. J. Cell. Physiol. 180:263–270, 1999. © 1999 Wiley-Liss, Inc. 相似文献
43.
Lodovico Di Gioia Bernard Cuq Stphane Guilbert 《International journal of biological macromolecules》1999,24(4):5762-350
Thermal properties of corn gluten meal (CGM) and of its extracted proteic components (zein and glutelin) at 0% moisture content, is studied by dynamic mechanical thermal analysis (DMTA) and modulated differential scanning calorimetry (MDSC). The glass transition temperature (Tg) on first heating, is measured at 176 and 174°C, respectively, for hot-air-dried and native CGM. For zein and glutelin isolated fractions, the measured Tg values are 164 and 209°C, respectively. The calculated Tg from using Matveev’s method (Matveev YI. Spec Publ R Soc Chem 1995;156;552) is in good agreement with experimental data for zein, a well defined protein. MDSC allows the measurement of change in heat capacity at Tg (ΔCp) with a single heating scan, avoiding sample alteration, and ΔCp values are 0.365 J/g per K for zein and 0.184 J/g per K for glutelin. The differences observed in Tg, relaxation temperatures, ΔCp and tan δ peak height are related to differences in the structure of the proteins, through the cross-linkages and hydrogen or van der Waals interactions. Experimental data from DMTA and MDSC, and the Couchman–Karasz thermodynamic approach indicate that CGM behaves as a miscible blend of its components, with high non-polar interactions between zein and glutelin proteins. 相似文献
44.
We present the results of two 1.2 ns molecular dynamics (MD) unfolding simulations on hen egg lysozyme in water at 300K, performed using a new procedure called PEDC (Path Exploration With Distance Constraints). This procedure allows exploration of low energy structures as a function of increasing RMSD from the native structure, and offers especially the possibility of extensive exploration of the conformational space during the initial unfolding stages. The two independent MD simulations gave similar chronology of unfolding events: disruption of the active site, kinking of helix C, partial unfolding of the three-stranded beta-sheet to a two-stranded sheet (during which the helices A, B, and D remain to a great extent native), and finally unfolding of the beta-domain and partial unfolding of the alpha-domain in which hydrophobic clusters persist. We show particularly that the loss of hydrophobic contacts between the beta-sheet turn residues Leu55 and Ile56 and the hydrobic patch of the alpha-domain destabilizes the beta-domain and leads to its unfolding, suggesting that the correct embedding of these residues in the alpha-beta interface may constitute the rate limiting step in folding. These results are in accord with experimental observations on the folding/unfolding behavior of hen egg lysozyme at room temperature. They would also explain the loss of stability and the tendency to aggregation observed for the mutant Leu55Thr, and the slow refolding kinetics observed in the analogous amyloidogenic variant of human lysozyme. 相似文献
45.
Galli GL Skovgaard N Abe AS Taylor EW Wang T 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2005,175(3):201-208
The functional role of nitric oxide (NO) was investigated in the systemic and pulmonary circulations of the South American rattlesnake, Crotalus durissus terrificus. Bolus, intra-arterial injections of the NO donor, sodium nitroprusside (SNP) caused a significant systemic vasodilatation resulting in a reduction in systemic resistance (Rsys). This response was accompanied by a significant decrease in systemic pressure and a rise in systemic blood flow. Pulmonary resistance (Rpul) remained constant while pulmonary pressure (Ppul) and pulmonary blood flow (Qpul) decreased. Injection of L-Arginine (L-Arg) produced a similar response to SNP in the systemic circulation, inducing an immediate systemic vasodilatation, while Rpul was unaffected. Blockade of NO synthesis via the nitric oxide synthase inhibitor, L-NAME, did not affect haemodynamic variables in the systemic circulation, indicating a small contribution of NO to the basal regulation of systemic vascular resistance. Similarly, Rpul and Qpul remained unchanged, although there was a significant rise in Ppul. Via injection of SNP, this study clearly demonstrates that NO causes a systemic vasodilatation in the rattlesnake, indicating that NO may contribute in the regulation of systemic vascular resistance. In contrast, the pulmonary vasculature seems far less responsive to NO. 相似文献
46.
Alexander Jackson Benedicte B. Guilbert Stuart D. Plant Julian Goggi Mark R. Battle John L. Woodcraft Alessandra Gaeta Clare L. Jones Denis R. Bouvet Paul A. Jones Dennis M. O’Shea Penny Hao Zheng Samantha L. Brown Amanda L. Ewan William Trigg 《Bioorganic & medicinal chemistry letters》2013,23(3):821-826
Positron emission tomography (PET) using the tracer [11C]Flumazenil has shown changes in the distribution and expression of the GABAA receptor in a range of neurological conditions and injury states. We aim to develop a fluorine-18 labelled PET agent with comparable properties to [11C]Flumazenil. In this study we make a direct comparison between the currently known fluorine-18 labelled GABAA radiotracers and novel imidazobenzodiazepine ligands. A focussed library of novel compound was designed and synthesised where the fluorine containing moiety and the position of attachment is varied. The in vitro affinity of twenty-two compounds for the GABAA receptor was measured. Compounds containing a fluoroalkyl amide or a longer chain ester group were eliminated due to low potency. The fluorine-18 radiochemistry of one compound from each structural type was assessed to confirm that an automated radiosynthesis in good yield was feasible. Eleven of the novel compounds assessed appeared suitable for in vivo assessment as PET tracers. 相似文献
47.
48.
Johnstone ED Sawicki G Guilbert L Winkler-Lowen B Cadete VJ Morrish DW 《Proteomics》2011,11(20):4077-4084
Proteomics were performed using highly (99.99%) purified cytotrophoblasts from six normal and six pre-eclamptic placentas. Eleven proteins were found which decreased in pre-eclampsia (actin, glutathione S-transferase, peroxiredoxin 6, aldose reductase, heat shock protein 60 (Hsp60), two molecular forms of heat shock protein 70 (Hsp70) β-tubulin, subunit proteasome, ezrin, protein disulfide isomerase, and phosphoglycerate mutase 1). Only one protein, α-2-HS-glycoprotein (fetuin), was found to increase its expression. Western blots of actin, Hsp70, ezrin, and glutatione S-transferase confirmed decrease in protein expression. Many of the proteins that decreased are consistent with a state of oxidative stress in the pre-eclamptic placenta and a decreased cytotrophoblast defense against and response to oxidative stress. 相似文献
49.
Andrea LJ Marschall Congcong Zhang André Frenzel Thomas Schirrmann Michael Hust Franck Perez Stefan Dübel 《MABS-AUSTIN》2014,6(4):943-956
The use of antibodies to target their antigens in living cells is a powerful analytical tool for cell biology research. Not only can molecules be localized and visualized in living cells, but interference with cellular processes by antibodies may allow functional analysis down to the level of individual post-translational modifications and splice variants, which is not possible with genetic or RNA-based methods. To utilize the vast resource of available antibodies, an efficient system to deliver them into the cytosol from the outside is needed. Numerous strategies have been proposed, but the most robust and widely applicable procedure still remains to be identified, since a quantitative ranking of the efficiencies has not yet been done. To achieve this, we developed a novel efficiency evaluation method for antibody delivery based on a fusion protein consisting of a human IgG1 Fc and the recombination enzyme Cre (Fc-Cre). Applied to suitable GFP reporter cells, it allows the important distinction between proteins trapped in endosomes and those delivered to the cytosol. Further, it ensures viability of positive cells and is unsusceptible to fixation artifacts and misinterpretation of cellular localization in microscopy and flow cytometry. Very low cytoplasmic delivery efficiencies were found for various profection reagents and membrane penetrating peptides, leaving electroporation as the only practically useful delivery method for antibodies. This was further verified by the successful application of this method to bind antibodies to cytosolic components in living cells. 相似文献
50.
Jérôme Murienne Philippe Grandcolas Maria Dolors Piulachs Xavier Bellés Cyrille D'Haese Frédéric Legendre Roseli Pellens Eric Guilbert 《Cladistics : the international journal of the Willi Hennig Society》2005,21(1):2-7
New Caledonia is well known as a hot spot of biodiversity whose origin as a land mass can be traced back to the Gondwanan supercontinent. The local flora and fauna, in addition to being remarkably rich and endemic, comprise many supposedly relictual groups. Does the New Caledonian biota date back to Gondwanan times, building up its richness and endemism over 100 Myr or does it result from recent diversifications after Tertiary geological catastrophic events? Here we use a molecular phylogenetic approach to answer this question with the study of the Neocaledonian cockroach genus Angustonicus belonging to the subfamily Tryonicinae from Australia and New Caledonia. Both geological and molecular dating show that the diversification of this group is less than two million years old, whatever the date of its origin itself. This dating is not consistent with hypotheses of Gondwanan richness and endemism in New Caledonian biota. In other terms, local richness and endemism at the specific level are not necessarily related to an old Gondwanan origin of the Neocaledonian groups. © The Willi Hennig Society 2005. 相似文献