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While it has long been recognized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild-type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay. 相似文献
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Elizabeth A. Hunt Jordan M. Duval-Arnould Kristen L. Nelson-McMillan Jamie Haggerty Bradshaw Marie Diener-West Julianne S. Perretta Nicole A. Shilkofski 《Resuscitation》2014
Introduction
Previous studies reveal pediatric resident resuscitation skills are inadequate, with little improvement during residency. The Accreditation Council for Graduate Medical Education highlights the need for documenting incremental acquisition of skills, i.e. “Milestones”. We developed a simulation-based teaching approach “Rapid Cycle Deliberate Practice” (RCDP) focused on rapid acquisition of procedural and teamwork skills (i.e. “first-five minutes” (FFM) resuscitation skills). This novel method utilizes direct feedback and prioritizes opportunities for learners to “try again” over lengthy debriefing.Participants
Pediatric residents from an academic medical center.Methods
Prospective pre-post interventional study of residents managing a simulated cardiopulmonary arrest. Main outcome measures include: (1) interval between onset of pulseless ventricular tachycardia to initiation of compressions and (2) defibrillation.Results
Seventy pediatric residents participated in the pre-intervention and fifty-one in the post-intervention period. Baseline characteristics were similar. The RCDP-FFM intervention was associated with a decrease in: no-flow fraction: [pre: 74% (5–100%) vs. post: 34% (26–53%); p < 0.001)], no-blow fraction: [pre: 39% (22–64%) median (IQR) vs. post: 30% (22–41%); p = 0.01], and pre-shock pause: [pre: 84 s (26–162) vs. post: 8 s (4–18); p < 0.001]. Survival analysis revealed RCDP-FFM was associated with starting compressions within 1 min of loss of pulse: [Adjusted Hazard Ratio (HR): 3.8 (95% CI: 2.0–7.2)] and defibrillating within 2 min: [HR: 1.7 (95% CI: 1.03–2.65)]. Third year residents were significantly more likely than first years to defibrillate within 2 min: [HR: 2.8 (95% CI: 1.5–5.1)].Conclusions
Implementation of the RCDP-FFM was associated with improvement in performance of key measures of quality life support and progressive acquisition of resuscitation skills during pediatric residency. 相似文献137.
Walla P 《Progress in neurobiology》2008,84(2):192-209
The article specifies several important aspects related to the sense of smell in vertebrates. The idea that odors exert effects in the human brain though being not consciously perceived is introduced. Functional aspects related to cross-modal sensory interaction between olfaction and vision are highlighted. In particular, studies making use of electrophysiological methods providing high temporal resolution reveal an early processing stage around 300 ms and a later stage around 700 ms after stimulus onset. The early stage has been associated with subconscious olfactory information processing, whereas the later stage most likely reflects conscious odor perception. Specific interactions are described between olfaction and language and between olfaction and face processing in correlation with both stages of olfactory information processing. A consciously perceived odor can negatively affect language and face processing if these stimuli are presented and associated simultaneously, whereas simultaneous subconscious odor processing has the potential to improve memory formation in other stimulus modalities. Strikingly, the subconscious effect seems not to depend on odor valence. Besides a better understanding of the sense of olfaction itself, these findings on cross-modal integration support the idea that neural representations exist for semantic contents (object meaning) independent from particular sensory modalities. These representations can be referred to as meta representations because the information they contain is derived from a great variety of sensory information integrated into a semantic representation of an object. It is suggested that such meta representations represent the basic units for cognition and that they provide inputs during dreaming. 相似文献
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Circadian expression and functional characterization of PEA‐15 within the mouse suprachiasmatic nucleus
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Kelin Wheaton Sydney Aten Lucas Sales Queiroz Kyle Sullivan John Oberdick Kari R. Hoyt Karl Obrietan 《The European journal of neuroscience》2018,47(7):845-857
The circadian timing system influences the functional properties of most, if not all, physiological processes. Central to the mammalian timing system is the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN functions as a ‘master clock’ that sets the phasing of ancillary circadian oscillator populations found throughout the body. Further, via an entraining input from the retina, the SCN ensures that the clock oscillators are synchronized to the daily light/dark cycle. A critical component of the SCN timing and entrainment systems is the p44/42 mitogen‐activated protein kinase (ERK/MAPK) pathway. Here, we examined the expression and function of phosphoprotein‐enriched in astrocytes (PEA‐15), an ERK scaffold protein that serves as a key regulator of MAPK signaling. A combination of immunolabeling and Western blotting approaches revealed high levels of PEA‐15 within the SCN. PEA‐15 expression was enriched in distinct subpopulations of SCN neurons, including arginine vasopressin (AVP)‐positive neurons of the SCN shell region. Further, expression profiling detected a significant circadian oscillation in PEA‐15 expression within the SCN. Brief photic stimulation during the early subjective night led to a significant increase in PEA‐15 phosphorylation, an event that can trigger ERK/PEA‐15 dissociation. Consistent with this, co‐immunoprecipitation assays revealed that PEA‐15 is directly bound to ERK in the SCN and that photic stimulation leads to their dissociation. Finally, we show that PEA‐15 regulates ERK/MAPK‐dependent activation of the core clock gene period1. Together, these data raise the prospect that PEA‐15 functions as a key regulator of the SCN timing system. 相似文献
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Voltage gradients in transvenous and subcutaneous defibrillation and their risk of myocardial damage
Andres Belalcazar PhD Wyatt Stahl BS Daniel J. Friedman MD Tom F. Brouwer MD Reinoud E. Knops MD PhD Jeanne E. Poole MD E. Kevin Heist MD PhD 《Journal of cardiovascular electrophysiology》2023,34(7):1561-1568