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91.
A. Grammenos A. Mouithys-Mickalad M. Lismont M. Hoebeke 《Biochemical and biophysical research communications》2010,398(3):350-8062
A new way to study the action of cyclodextrin was developed to quantify the damage caused on cell membrane and lipid bilayer. The Electron Spin Resonance (ESR) spectroscopy was used to study the action of Randomly methylated-beta-cyclodextrin (Rameb) on living cells (HCT-116). The relative anisotropy observed in ESR spectrum of nitroxide spin probe (5-DSA and cholestane) is directly related to the rotational mobility of the probe, which can be further correlated with the microviscosity. The use of ESR probes clearly shows a close correlation between cholesterol contained in cells and cellular membrane microviscosity. This study also demonstrates the Rameb ability to extract cholesterol and phospholipids in time- and dose-dependent ways. In addition, ESR spectra enabled to establish that cholesterol is extracted from lipid rafts to form stable aggregates. The present work supports that ESR is an easy, reproducible and noninvasive technique to study the effect of cyclodextrins on cell membranes. 相似文献
92.
Ute Möllmann Lothar Heinisch Adolf Bauernfeind Thilo Köhler Dorothe Ankel-Fuchs 《Biometals》2009,22(4):615-624
The outer membrane permeability barrier is an important resistance factor of bacterial pathogens. In combination with drug
inactivating enzymes, target alteration and efflux, it can increase resistance dramatically. A strategy to overcome this membrane-mediated
resistance is the misuse of bacterial transport systems. Most promising are those for iron transport. They are vital for virulence
and survival of bacteria in the infected host, where iron depletion is a defense mechanism against invading pathogens. We
synthesized biomimetic siderophores as shuttle vectors for active transport of antibiotics through the bacterial membrane.
Structure activity relationship studies resulted in siderophore aminopenicillin conjugates that were highly active against
Gram-negative pathogens which play a crucial role in destructive lung infections in cystic fibrosis patients and in severe
nosocomial infections. The mechanism of action and the uptake of the compounds via specific iron siderophore transport routes
were demonstrated. The novel conjugates were active against systemic Pseudomonas aeruginosa infections in mice with ED50 values comparable to the quinolone ofloxacin and show low toxicity. 相似文献
93.
94.
J. Adam Hendricks Robert N. Hanson Michael Amolins John M. Mihelcic Brian S. Blagg 《Bioorganic & medicinal chemistry letters》2013,23(12):3635-3639
Three novel steroidal antiestrogen–geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11β-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity. 相似文献
95.
Extracts of mature silver fir (Abies alba Mill.) needles, current-year, and one-year old (A) and seven to nine-year old (B), were purified by reversed and normal phase HPLC. Gibberellin (GA)-like compounds were detected by the Tan-ginbozu dwarf rice micro-drop bioassay and corresponding fractions were analyzed by GC-MS. GA9 was present in small amounts, while a major component was a cellulase-hydrolysable GA9 conjugate which was assumed to be GA9 glucosyl ester. It is proposed that GA9 glucosyl ester plays a key role in the regulation of endogenous GA levels in silver fir needles. 相似文献
96.
M. P. Filatova O. V. Kotel’nikova O. V. Chibiskova O. E. Lakhtina V. A. Nesmeyanov A. P. Alliluev D. O. Koroev M. A. Titova T. D. Volkova O. M. Vol’pina V. T. Ivanov 《Russian Journal of Bioorganic Chemistry》2008,34(5):563-570
A new approach to the development of a vaccine against meningococci of serogroups A and B was proposed. It involves the synthesis of conjugates of high-molecular capsule polysaccharides of the serogroup A meningococcus (PsA) with earlier synthesized protective fragments of membrane proteins from serogroup B meningococci. The conjugates were synthesized using a method that consists of the generation of aldehyde groups by oxidizing free vicinal hydroxyl groups of PsA and subsequent reaction of these groups with amino groups of the peptide. The reaction proceeds with the intermediate formation of the Schiff base, which is reduced to the stable secondary amine. The main parameters of the reaction were optimized in the synthesis of a PsA conjugate with a model peptide and methods of their characterization were developed. The reproducibility and efficiency of the synthetic procedure were demonstrated by the example of synthesis of PsA conjugates with fragments of protein PorA from the outer membrane of the serogroup B meningococcus. It was shown that, when administered without adjuvant, a conjugate of PsA with a protective peptide, which represents an exposed conserved fragment 306–332 of protein PorA, stimulates the formation of antibodies to the peptide and polysaccharide moieties of the molecule and is also capable of decreasing the degree of bacteremia in animals infected with serogroup A and serogroup B meningococci. The approach can be applied to the development of a complex vaccine for serogroup A and serogroup B meningococci. 相似文献
97.
Siva S. Panda Mohamed A. Ibrahim Said A. El‐Feky Alan R. Katritzky 《Journal of peptide science》2013,19(2):110-117
Nα‐Boc‐Nim‐(4‐toluenesulfonyl‐l ‐histidylbenzotriazole) enables convenient acylation of N‐, O‐, S‐, and C‐nucleophiles with no detectable racemization. We report efficient syntheses of novel histidine‐containing di‐, tri‐, and tetra‐peptides and models for the preparation of potentially biologically active histidine N‐, O‐, S‐, and C‐conjugates. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
98.
The plant hormone auxin (indole-3-acetic acid, IAA) is involved in the control of many phenomena during plant development. By characterizing steady-state free and conjugated IAA levels using a stable isotope dilution method coupled with gas chromatography- selected ion monitoring- mass spectrometry, this paper provides a detailed characterization of IAA metabolism in five liverworts, four mosses, and two tracheophytes. Long-term IAA conjugation patterns were monitored by incubating actively growing tissue with (14)C-IAA and then analyzing the de novo synthesis of IAA conjugates with radioimaging techniques. The liverworts, mosses, and tracheophytes can be differentiated by the total amount of IAA metabolites, the proportion of free and conjugated IAA, the chemical nature of their IAA conjugates, and the rates of IAA conjugation. Our tentative conclusion is that the liverworts appear to employ a biosynthesis-degradation strategy for the regulation of free IAA levels, in contrast to the conjugation-hydrolysis strategy apparently used by the mosses and tracheophytes. Such alternative metabolic strategies may have profound implications for macroevolutionary processes in these plant groups. 相似文献
99.
E. David Morgan Colin R. Bielby Ian D. Wilson 《Journal of experimental marine biology and ecology》2005,321(2):125-134
An analytical procedure for the quantification of ecdysteroids (crustacean moulting hormone) in barnacles was devised so that minimum sample size could be used. A combination of solvent partitions, Sephadex chromatography, silylation and gas chromatography with electron capture detection was devised, enabling ecdysteroids to be determined down to 20 pg. This was used to determine the amount of moulting hormone in a population of barnacles over a 30 month period. Levels varied from barely detectable in winter months to a maximum value of 1.5 μg kg− 1 of wet weight of barnacles in September. Polar conjugates of 20-hydroxyecdysone were detected only during the winter months. The number of barnacles moulting at any time corresponded roughly to the titre of hormone present at that time. 相似文献
100.
Indalecio Quesada‐Soriano Lorien J. Parker Alessandra Primavera Juan M. Casas‐Solvas Antonio Vargas‐Berenguel Carmen Barón Craig J. Morton Anna Paola Mazzetti Mario Lo Bello Michael W. Parker Luis García‐Fuentes 《Protein science : a publication of the Protein Society》2009,18(12):2454-2470
The effect of the Y108V mutation of human glutathione S‐transferase P1‐1 (hGST P1‐1) on the binding of the diuretic drug ethacrynic acid (EA) and its glutathione conjugate (EASG) was investigated by calorimetric, spectrofluorimetric, and crystallographic studies. The mutation Tyr 108 → Val resulted in a 3D‐structure very similar to the wild type (wt) enzyme, where both the hydrophobic ligand binding site (H‐site) and glutathione binding site (G‐site) are unchanged except for the mutation itself. However, due to a slight increase in the hydrophobicity of the H‐site, as a consequence of the mutation, an increase in the entropy was observed. The Y108V mutation does not affect the affinity of EASG for the enzyme, which has a higher affinity (Kd ~ 0.5 μM) when compared with those of the parent compounds, K ~ 13 μM, K ~ 25 μM. The EA moiety of the conjugate binds in the H‐site of Y108V mutant in a fashion completely different to those observed in the crystal structures of the EA or EASG wt complex structures. We further demonstrate that the ΔCp values of binding can also be correlated with the potential stacking interactions between ligand and residues located in the binding sites as predicted from crystal structures. Moreover, the mutation does not significantly affect the global stability of the enzyme. Our results demonstrate that calorimetric measurements maybe useful in determining the preference of binding (the binding mode) for a drug to a specific site of the enzyme, even in the absence of structural information. 相似文献