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The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.  相似文献   
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We investigated the effects of plant growth regulators [6-benzyladenine (BA), kinetin (Kin), 6-γ,γ-dimethylallylaminopurine (2iP), thidiazuron (TDZ) and α-naphthaleneacetic acid (NAA)], modified Murashige and Skoog (MS) medium containing 10 mM NH4 + and 5 mM NO3 and supplemented with 2iP, BA, Kin and NAA (MSM medium), and two elicitors [jasmonic acid (JA), and salicylic acid (SA)], on plant growth and accumulation of hypericins (hypericin and pseudohypericin) and hyperforin in shoot cultures of Hypericum hirsutum and H. maculatum. Our data suggested that culture of shoots on MS medium supplemented with BA (0.4 mg l−1) or Kin (0.4 mg l−1) enhanced production of hypericins in H. maculatum and hyperforin in H. hirsutum. Hypericins and hyperforin concentrations decreased in both species when TDZ (0.4 mg l−1) was added to the MS medium. Also, TDZ induced hyperhydric malformations and necrosis of regenerated shoots. Cultivation of H. maculatum on MSM medium resulted in approximately twofold increased production of hypericins compared to controls, and the growth of H. hirsutum shoots on the same medium led to a 6.16-fold increase in hyperforin production. Of the two elicitors, SA was more effective in stimulating the accumulation of hypericins. At 50 μM, SA enhanced the production of hypericin (7.98-fold) and pseudohypericin (13.58-fold) in H. hirsutum, and, at 200 μM, enhanced the production of hypericin (2.2-fold) and pseudohypericin (3.94-fold) in H. maculatum.  相似文献   
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The consumption of monosodium glutamate (MSG) is advocated to elicit physiological and metabolic effects, yet these effects have been poorly investigated directly in humans and in particular in the postprandial phase. Thirteen healthy adults were supplemented for 6 days with a nutritional dose of MSG (2 g) or sodium chloride (NaCl) as control, following a crossover design. On the 7th day, they underwent a complete postprandial examination for the 6 h following the ingestion of the same liquid standard meal (700 kcal, 20% of energy as [(15)N]protein, 50% as carbohydrate, and 30% as fat) supplemented with MSG or NaCl. Real-ultrasound measures of antral area indicated a significant increased distension for the 2 h following the meal supplemented with MSG vs. NaCl. This early postprandial phase was also associated with significantly increased levels of circulating leucine, isoleucine, valine, lysine, cysteine, alanine, tyrosine, and tryptophan after MSG compared with NaCl. No changes to the postprandial glucose, insulin, glucagon-like peptide (GLP)-1, and ghrelin were noted between MSG- and NaCl-supplemented meals. Subjective assessments of hunger and fullness were neither affected by MSG supplementation. Finally, the postprandial fate of dietary N was identical between dietary conditions. Our findings indicate that nutritional dose of MSG promoted greater postprandial elevations of several indispensable amino acids in plasma and induced gastric distension. Further work to elucidate the possible sparing effect of MSG on indispensable amino acid first-pass uptake in humans is warranted. This trial was registered at clinicaltrials.gov as NCT00862017.  相似文献   
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Electrical responses of olfactory sensory neurons to odorants were examined in the presence of zinc nanoparticles of various sizes and degrees of oxidation. The zinc nanoparticles were prepared by the underwater electrical discharge method and analyzed by atomic force microscopy and X-ray photoelectron spectroscopy. Small (1.2 ± 0.3 nm) zinc nanoparticles significantly enhanced electrical responses of olfactory neurons to odorants. After oxidation, however, these small zinc nanoparticles were no longer capable of enhancing olfactory responses. Larger zinc oxide nanoparticles (15 nm and 70 nm) also did not modulate responses to odorants. Neither zinc nor zinc oxide nanoparticles produced olfactory responses when added without odorants. The enhancement of odorant responses by small zinc nanoparticles was explained by the creation of olfactory receptor dimers initiated by small zinc nanoparticles. The results of this work will clarify the mechanisms for the initial events in olfaction, as well as to provide new ways to alleviate anosmia related to the loss of olfactory receptors.  相似文献   
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The currative properties of aromatic and medicinal plants have been recognized since ancient times and, more recently, the antimicrobial activity of plant essential oils has been used in several applications, including food preservation. The purpose of this study was to create directly comparable, quantitative data on the antimicrobial activity of some plant essential oils prepared in the National Institute of Research-Development for Chemistry and Petrochemistry, Bucharest to be used for the further development of food packaging technology, based on their antibacterial and antifungal activity. The essential oils extracted from thyme (Thymus vulgaris L.), basil (Ocimum basilicum L.), coriander (Coriandrum sativum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.), fennel (Foeniculum vulgare L.), spearmint (Mentha spicata L.) and carraway (Carum carvi L.) were investigated for their antimicrobial activity against eleven different bacterial and three fungal strains belonging to species reported to be involved in food poisoning and/or food decay: S. aureus ATCC 25923, S. aureus ATCC 6538, S. aureus ATCC 25913, E. coli ATCC 25922, E. coli ATCC 35218, Salmonella enterica serovar Enteritidis Cantacuzino Institute Culture Collection (CICC) 10878, Listeria monocytogenes ATCC 19112, Bacillus cereus CIP 5127, Bacillus cereus ATCC 11778, Candida albicans ATCC 10231, Aspergillus niger ATCC 16404, Penicillium spp. CICC 251 and two E. coli and Salmonella enterica serovar Enteritidis clinical isolates. The majority of the tested essential oils exibited considerable inhibitory capacity against all the organisms tested, as supported by growth inhibition zone diameters, MICs and MBC's. Thyme, coriander and basil oils proved the best antibacterial activity, while thyme and spearmint oils better inhibited the fungal species.  相似文献   
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