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81.
Corticospinal axon outgrowth in vivo and the ability to sprout or regenerate after injury decline with age. This developmental decline in growth potential has been correlated with an increase in inhibitory myelin-associated proteins in older spinal cord. However, previous results have shown that sprouting of corticospinal fibers after contralateral lesions begins to diminish prior to myelination, suggesting that a decrease in growth promoting and/or an increase in inhibitory molecules in spinal gray matter may also regulate corticospinal axon outgrowth. To address this possibility, we carried out in vitro experiments to measure neurite outgrowth from explants of 1-day-old hamster forelimb sensorimotor cortex that were plated onto membrane carpets or membrane stripe assays prepared from white or gray matter of 1-to 22-day-old cervical spinal cord. On uniform carpets and in the stripe assays cortical neurites grew robustly on young but not older membranes from both white and gray matter. Mixtures of membranes from 1- and 15-day spinal cord inhibited neurite outgrowth, suggesting that the presence of inhibitory molecules in the 15-day cord overwhelmed permissive or growth promoting molecules in membranes from 1-day cord. Video microscopic observations of growth cone behaviors on membrane stripe assays transferred to glass coverslips supported this view. Cortical growth cones repeatedly collapsed at borders between permissive substrates (laminin or young membrane stripes) and nonpermissive substrates (older membrane stripes). Growth cones either turned away from the older membranes or reduced their growth rates. These results suggest that molecules in both the gray and white matter of the developing spinal cord can inhibit cortical neurite outgrowth. 相似文献
82.
Juliana M Sousa-Canavez Flavio C Canavez Kátia RM Leite Luiz H Camara-Lopes 《Genetic vaccines and therapy》2008,6(1):1-7
Background
Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.Methods
Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.Results
Experiments confirm that electroporation alone is more effective in enhancing reporter gene expression than plasmid injection alone, plasmid conjugation with liposomes followed by injection, or than the combination of liposomes and electroporation. However, with two time courses of multiple electrically-mediated plasmid deliveries, neither the levels nor duration of transgene expression are significantly increased. Tissue damage may increase following a second treatment, no further damage is observed after a third treatment. When electroporation conditions utilized in a mouse model are tested in thicker rat skin, only higher field strengths or longer pulses were as effective in plasmid delivery.Conclusion
Electroporation enhances reporter plasmid delivery to the skin to a greater extent than the liposome conjugation method tested. Multiple deliveries do not necessarily result in higher or longer term expression. In addition, some impact on tissue integrity with respect to surface damage is observed. Pulsing conditions should be optimized for the model and for the expression profile desired. 相似文献83.
Kelly E. Radziwon Kristie M. June Daniel J. Stolzberg Matthew A. Xu-Friedman Richard J. Salvi Micheal L. Dent 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2009,195(10):961-969
Tone detection and temporal gap detection thresholds were determined in CBA/CaJ mice using a Go/No-go procedure and the psychophysical
method of constant stimuli. In the first experiment, audiograms were constructed for five CBA/CaJ mice. Thresholds were obtained
for eight pure tones ranging in frequency from 1 to 42 kHz. Audiograms showed peak sensitivity between 8 and 24 kHz, with
higher thresholds at lower and higher frequencies. In the second experiment, thresholds for gap detection in broadband and
narrowband noise bursts were measured at several sensation levels. For broadband noise, gap thresholds were between 1 and
2 ms, except at very low sensation levels, where thresholds increased significantly. Gap thresholds also increased significantly
for low pass-filtered noise bursts with a cutoff frequency below 18 kHz. Our experiments revised absolute auditory thresholds
in the CBA/CaJ mouse strain and demonstrated excellent gap detection ability in the mouse. These results add to the baseline
behavioral data from normal-hearing mice which have become increasingly important for assessing auditory abilities in genetically
altered mice. 相似文献
84.
The fungal cyanide hydratases form a functionally specialized subset of the nitrilases which catalyze the hydrolysis of cyanide
to formamide with high specificity. These hold great promise for the bioremediation of cyanide wastes. The low resolution
(3.0 nm) three-dimensional reconstruction of negatively stained recombinant cyanide hydratase fibers from the saprophytic
fungus Neurospora crassa by iterative helical real space reconstruction reveals that enzyme fibers display left-handed D1 S5.4 symmetry with a helical rise of 1.36 nm. This arrangement differs from previously characterized microbial nitrilases which
demonstrate a structure built along similar principles but with a reduced helical twist. The cyanide hydratase assembly is
stabilized by two dyadic interactions between dimers across the one-start helical groove. Docking of a homology-derived atomic
model into the experimentally determined negative stain envelope suggests the location of charged residues which may form
salt bridges and stabilize the helix. 相似文献
85.
86.
Multiple histone-modifying enzymes have been identified in the past several years. Much has been learned regarding the biochemistry of these enzymes and their effects on gene expression in cultured cells. However, the functions of these factors during development are still largely unknown. Recent genetic studies indicate that specific histone modifications and modifying enzymes play essential roles in both global and tissue-specific chromatin organization. In particular, these studies indicate that enzymes that control levels and patterns of histone acetylation and methylation are required for normal embryo patterning, organogenesis, and survival. 相似文献
87.
Huck BR Llamas L Robarge MJ Dent TC Song J Hodnick WF Crumrine C Stricker-Krongrad A Harrington J Brunden KR Bennani YL 《Bioorganic & medicinal chemistry letters》2006,16(15):4130-4134
5-HT2C agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT2C agonists. SAR was developed around this chemotype and compounds were identified that were potent (Ki<15 nM) and selective relative to other 5-HT2 receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats. 相似文献
88.
89.
90.
Melissa R. Dent Paramjit S. Tappia Naranjan S. Dhalla 《Journal of cellular physiology》2011,226(1):181-186
This study was undertaken to determine alterations in the β‐adrenoceptor (β‐AR) signaling system in male and female rats at 4 weeks after the induction of arteriovenous (AV) fistula or shunt. AV shunt produced a greater degree of cardiac hypertrophy and larger increase in cardiac output in male than in female animals. Increases in plasma levels of norepinephrine and epinephrine (EPI) due to AV shunt were also higher in male than females. While no difference in the β1‐AR affinity was seen in males and females, AV shunt induced increase in β1‐AR density in female rats was higher than that in males. Furthermore, no changes in basal adenylyl cyclase (AC) V/VI mRNA levels were seen; however, the increase in EPI‐stimulated AC activities was greater in AV shunt females than in males. AV shunt decreased myocardial β1‐AR mRNA level in male rats and increased β2‐AR mRNA level in female hearts; an increase in Gi‐protein mRNA was detected only in male hearts. Although GRK2 gene expression was increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt female rats. β‐arrestin1 mRNA was elevated in females whereas β‐arrestin 2 gene expression was increased in both male and female AV shunt rats. While these data demonstrate gender associated differences in various components of the β‐AR system in cardiac hypertrophy due to AV shunt, only higher levels of plasma catecholamines may account for the greater increase in cardiac output and higher degree of cardiac hypertrophy in males. J. Cell. Physiol. 226: 181–186, 2010. © 2010 Wiley‐Liss, Inc. 相似文献