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41.
J. Davies R.H. Evans P.L. Herrling A.W. Jones H.J. Olverman P. Pook J.C. Watkins 《Brain research》1986,382(1):169-173
Properties of a new potent antagonist acting selectively at N-methyl-D-aspartate (NMDA) type excitatory amino acid receptors are described. This compound, 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) is more potent than all previously reported NMDA antagonists in depressing mammalian spinal neuronal responses (cat and immature rat), in its affinity for [3H]D-AP5 (a radiolabelled NMDA antagonist) binding sites on rat brain membranes, and as an anticonvulsant in mice. 相似文献
42.
Glutamate-dopamine interactions in the basal ganglia: relationship to Parkinson's disease 总被引:4,自引:0,他引:4
J. T. Greenamyre 《Journal of neural transmission (Vienna, Austria : 1996)》1993,91(2-3):255-269
Summary Current antiparkinsonian therapies focus on either replacing dopamine via precursor (L-DOPA) administration, or directly stimulating postsynaptic dopamine receptors with dopamine agonists. Unfortunately, this approach is associated with numerous side effects and these drugs lose efficacy with disease progression. This article reviews recent evidence which suggests that negative modulation of glutamatergic neurotransmission has antiparkinsonian effects in a variety of rodent and primate models of parkinsonism. The pronounced synergism between dopaminergic agents and glutamate receptor antagonists may provide a means of using very low doses of the two drug classes in concert to treat Parkinson's disease effectively and minimize dose-related drug side effects. 相似文献
43.
It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-
-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC. 相似文献
44.
Pretreatment with the antiemetic agent trimethobenzamide (TMB) prevented the hypophagic response of rats to acetyl salicylate
(a known emetic in man and dogs). However, it did not affect the hypophagic responses to the 5-HT1B agonist RU 24969, or to the 5-HT1C/5-HT1B agonistsmCPP and TFMPP. The results therefore suggest that the hypophagic effects of the 5-HT agonists do not involve a malaise-dependent
mechanism similar to that mediating the effect of acetyl salicylate. 相似文献
45.
The responses of ipsilateral medial vestibular nucleus (MVN) neurons in brainstem slices from guinea pigs compensated for a unilateral labyrinthectomy (UL), to the
(NMDA) receptor/channel antagonists CPP and MK801, were compared with those of MVN neurons in brainstem slices from labyrinthine-intact guinea pigs observed in a previous study. The average resting activity of ipsilateral MVN neurons from compensated animals was significantly higher than that for MVN neurons from labyrinthine-intact animals; however, there were no significant differences in the average magnitude of the decrease in firing rate from baseline in response to CPP or MK801 and the only significant difference in the number of responses was to MK801, where fewer ipsilateral MVN neurons from compensated animals responded with a decrease in firing rate. These results suggest that vestibular compensation is not associated with an up-regulation or increased affinity of NMDA receptors in the MVN ipsilateral to the UL. 相似文献
46.
47.
Panayotis K. Thanos Ronald Kim Jacob Cho Brenda J. Anderson George A. Bray John K. Robinson 《Physiology & behavior》2010,101(5):713-718
Background
Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains.Methods
OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions.Results
OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine.Conclusion
Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs. 相似文献48.
Ganghua Tang Xiaolan Tang Xinlu Wang 《Journal of labelled compounds & radiopharmaceuticals》2010,53(8):543-547
A fully automated synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) was carried out by a convenient three‐step, one‐pot procedure on the modified TRACERlab FXFN synthesizer, including [18F]fluorination of ethyl 4‐(trimethylammonium triflate)benzoate as the precursor, saponification of the ethyl 4‐[18F]fluorobenzoate with aqueous tetrapropylammonium hydroxide instead of sodium hydroxide, and conversion of 4‐[18F]fluorobenzoate salt ([18F]FBA) to [18F]SFB treated with N,N,N′,N′‐tetramethyl‐O‐(N‐succinimidyl)uranium tetrafluoroborate (TSTU). The purified [18F]SFB was used for the labeling of Tat membrane‐penetrating peptide (containing the Arg‐Lys‐Lys‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Arg‐Pro‐Leu‐Gly‐Leu‐Ala‐Gly‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu‐Glu sequence, [18F]CPP) through radiofluorination of lysine amino groups. The uncorrected radiochemical yields of [18F]SFB were as high as 25–35% (based on [18F]fluoride) (n=10) with a synthesis time of~40 min. [18F]CPP was produced in an uncorrected radiochemical yields of 10–20% (n=5) within 30 min (based on [18F]SFB). The radiochemical purities of [18F]SFB and [18F]CPP were greater than 95%. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
49.
The present research aimed at investigating the opioid-adenosine interaction on regional cerebral blood flow (rCBF). Therefore rCBF in the sensory cortex of morphine-naive and -dependent rats was measured using the laser-Doppler flowmetry technique. The results showed that adenosine (10(-5), 10(-4), 10(-3) M) significantly increased rCBF in morphine-dependent rats (MDR) (P < 0.01). This effect was inhibited by theophylline (5 x 10(-5) M). Also systemic naloxone (0.5, 1.5 and 3 mg/kg, s.c.) significantly increased rCBF in MDR and it was accompanied by elevated blood pressure and heart rate. Local adenosine (10(-4) M) significantly augmented naloxone (0.5 mg/kg)-induced increase in rCBF of MDR but had no significant effect on naloxone's (1.5 and 3 mg/kg) increasing effect on rCBF. Theophylline also has no effect on naloxone increasing effect on rCBF. These data suggest that adenosine receptors responsiveness increase in sensory cortex of MDR. Naloxone also highly increased rCBF of MDR that probably not interfere with adenosine receptors. Also, it seems that adenosine acts as a modulator in rCBF regulation of morphine-dependent and morphine withdrawal rats. 相似文献
50.
Yongzhuo Huang Yifan Jiang Huiyuan Wang Jianxin Wang Meong Cheol Shin Youngro Byun Huining He Yanqin Liang Victor C. Yang 《Advanced drug delivery reviews》2013
Cell-penetrating peptide (CPP)-mediated intracellular drug delivery system, often specifically termed as “the Trojan horse approach”, has become the “holy grail” in achieving effective delivery of macromolecular compounds such as proteins, DNA, siRNAs, and drug carriers. It is characterized by the unique cell- (or receptor-), temperature-, and payload-independent mechanisms, therefore offering potent means to improve poor cellular uptake of a variety of macromolecular drugs. Nevertheless, this “Trojan horse” approach also acts like a double-edged sword, causing serious safety and toxicity concerns to normal tissues or organs for in vivo application, due to lack of target selectivity of the powerful cell penetrating activity. To overcome this problem of potent yet non-selective penetration vs. targeting delivery, a number of “smart” strategies have been developed in recent years, including controllable CPP-based drug delivery systems based on various stimuli-responsive mechanisms. This review article provides a fundamental understanding of these smart systems, as well as a discussion of their real-time in vivo applicability. 相似文献