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1.
Childhood trauma is known to increase risk for emotional disorders and addiction. However, little is currently understood about the neurodevelopmental basis of these effects, or how genetic and epigenetic factors interact with the environment to shape the systems subserving emotionality. In this review, we discuss the use of rodent models of early life emotional experience to study these issues in the laboratory and present some of our pertinent findings. In rats, postnatal maternal separation can produce lasting increases in emotional behavior and stressor-reactivity, together with alterations in various brain neurotransmitter systems implicated in emotionality, including corticotropin-releasing factor, serotonin, norepinephrine, and glutamate. Genetic differences between inbred mouse strains have been exploited to further study how maternal behavior affects emotional development using techniques such as cross-fostering and generation of inter-strain hybrids. Together with our own recent data, the findings of these studies demonstrate the pervasive influence of maternal and social environments during sensitive developmental periods and reveal how genetic factors determine how these early life experiences can shape brain and behavior throughout life.  相似文献
2.
Wallerian degeneration of the distal stump of a severed peripheral nerve involves invasion by myelomonocytic cells, whose presence is necessary for destruction of myelin and for initiating mitosis in Schwann cells (Beuche and Friede, 1984). Degeneration of the distal ends of the axons themselves is assumed to occur by autolytic mechanisms. We describe a strain of mice (C57BL/6/Ola) in which leucocyte invasion is slow and sparse. In these mice, confirming Beuche and Friede, myelin removal is extremely slow. A new finding is that axon degeneration is also very slow. This is a consequence of lack of recruitment of myelomonocytic cells for if such recruitment is prevented in other mouse strains by a monoclonal antibody against the complement type 3 receptor (Rosen and Gordon, 1987) axon degeneration is again slowed. We have also, surprisingly, found that nerve regeneration in the C57BL/6/Ola mice is not impeded by the presence of largely intact axons in the distal stump and absence of recruited cells, myelin debris and the absence of Schwann cell mitosis.  相似文献
3.
The neurotropic mouse hepatitis viruses (MHV), in particular strain JHM (JHMV or MHV-4), cause experimental central nervous system demyelination that pathologically resembles multiple sclerosis, an important human demyelinating disease. The mechanism of JHMV-induced demyelination remains unclear, though its tropism for oligodendrocytes had led to the belief that JHMV causes demyelination by direct lysis of these myelin-producing cells. However, several studies have also implicated the involvement of immune responses in the demyelinating process. In this communication, we present evidence that generalized immunosuppression with gamma irradiation prevents JHMV-induced demyelination, a finding that was not limited to a particular strain of JHMV or to one strain of mouse. In addition, significant paralytic-demyelinating disease was restored to infected, irradiated mice after the adoptive transfer of nylon wool nonadherent splenic cells and appeared to be restricted by the major histocompatibility complex (MHC). These observations indicate that the principal mechanisms of JHMV-induced demyelination are most likely immunopathological.  相似文献
4.
Crain SM  Shen KF 《Brain research》2001,888(1):75-82
Our previous electrophysiologic studies on nociceptive types of dorsal root ganglion (DRG) neurons in culture demonstrated that extremely low fM-nM concentrations of morphine and many other bimodally-acting mu, delta and kappa opioid agonists can elicit direct excitatory opioid receptor-mediated effects, whereas higher (microM) opioid concentrations evoked inhibitory effects. Cotreatment with pM naloxone or naltrexone (NTX) plus fM-nM morphine blocked the excitatory effects and unmasked potent inhibitory effects of these low opioid concentrations. In the present study, hot-water-immersion tail-flick antinociception assays at 52 degrees C on mice showed that extremely low doses of morphine (ca. 0.1 microg/kg) can, in fact, elicit acute hyperalgesic effects, manifested by rapid onset of decreases in tail-flick latency for periods >3 h after drug administration. Cotreatment with ultra-low-dose NTX (ca. 1-100 pg/kg) blocks this opioid-induced hyperalgesia and unmasks potent opioid analgesia. The consonance of our in vitro and in vivo evidence indicates that doses of morphine far below those currently required for clinical treatment of pain may become effective when opioid hyperalgesic effects are blocked by coadministration of appropriately low doses of opioid antagonists. This low-dose-morphine cotreatment procedure should markedly attenuate morphine tolerance, dependence and other aversive side-effects.  相似文献
5.
On the number of neurons in the dentate gyrus of the rat   总被引:9,自引:0,他引:9  
We have estimated the number of dentate granule cells in Sprague-Dawley and Wistar rats at 1, 4 and 12 months of age. In Sprague-Dawley rats the number of granule cells is relatively constant throughout this period at about 1 million. In Wistar rats, on the other hand, there is a progressive increase in the number from about 700,000 at 1 month to 1 million at 4 months; thereafter the number declines to about 800,000 at 1 year. Estimates of the numbers of cells in the polymorphic zone that can be stained immunohistochemically for somatostatin, cholecystokinin, vasoactive-intestinal peptide, and glutamic acid decarboxylase show no appreciable differences in the two strains.  相似文献
6.
This work demonstrates technical approaches to high-quality magnetic resonance imaging (MRI) of small structures of the mouse brain in vivo. It turns out that excellent soft-tissue contrast requires the reduction of partial volume effects by using 3D MRI at high (isotropic) resolution with linear voxel dimensions of about 100–150 μm. The long T2* relaxation times at relatively low magnetic fields (2.35 T) offer the benefit of a small receiver bandwidth (increased signal-to-noise) at a moderate echo time which together with the small voxel size avoids visual susceptibility artifacts. For measuring times of 1–1.5 h both T1-weighted (FLASH) and T2-weighted (Fast Spin-Echo) 3D MRI acquisitions exhibit detailed anatomical insights in accordance with histological sections from a mouse brain atlas. Preliminary applications address the identification of neuroanatomical variations in different mouse strains and the use of Mn2+ as a T1 contrast agent for neuroaxonal tracing of fiber tracts within the mouse visual pathway.  相似文献
7.
Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone-coated nylon suture were studied over 7  days in Sprague–Dawley rats ( n =36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone-coated suture (e.g. total cerebral infarct volume at 24  h before any fatalities was 119.9±79.8  mm3 , cf. 183.0±36.5 mm3 , n =12 for each, P <0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone-coated suture was further studied in Wistar and Fischer-344 rats ( n =12 for each). Seventy-five per cent of the Wistar's died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer-344 rats were both significantly greater compared with Sprague-Dawley rats (e.g. total cerebral infarct volume at 24  h in the former was 253.6±25.4  mm3 , n =11, P <0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone-coated suture and the Fischer-344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.  相似文献
8.
An analysis of the genetics of alcohol intoxication in inbred mice   总被引:6,自引:0,他引:6  
We compared the behaviors of eight inbred mouse strains across 18 variables, using 11 behavioral assays, and gave ethanol (EtOH) as an intoxicant. Genetic influences on behavior and sensitivity to EtOH were pronounced, but strain sensitivities were generally only modestly correlated across tasks. Certain well-correlated clusters of responses suggested that some genes affect similar neurobiological substrates. No strains of mice were generally sensitive or resistant to intoxication across tasks. Anthropomorphically appealing concepts like ‘muscle strength’ had little explanatory power across tasks. A battery of selected tests was proposed for future studies. Overall, the results show that each mouse behavioral assay captures only a portion of ataxia, a genetically complex behavioral domain. Conversely, multiple behavioral capacities are apparently required for performance in each specific assay. Thus, if only one or two tests are used to evaluate motor function in genetically engineered mutant mice, only a small portion of the domain will be assessed and results may be misleading. This caveat likely extends to many behavioral domains (e.g. learning and memory, anxiety).  相似文献
9.
Gustatory neural responses in three different strains of mice   总被引:5,自引:0,他引:5  
Taste sensitivity in mice and its strain variation were studied by examining integrated responses and single fiber discharges of the chorda tympani nerve to various taste stimuli in the 3 different strains of mice (BALB, C3H and C57BL mice). A comparison among integrated responses of the 3 strains demonstrated that C57BL mice possess the highest sensitivity to sucrose and the lowest to acids, whereas the opposite is true for BALB mice. These 3 strains of mice commonly possess higher sensitivity to divalent chloride salts than to NaCl. Measures of the breadth of responsiveness showed that single fibers of all 3 strains of mice are relatively more narrowly tuned to taste stimuli than those of rats and hamsters, although the specificity of fibers tends to be greater in the order of C57BL greater than C3H greater than BALB mice. A cluster analysis of fibers demonstrated that two distinct fiber types, a sweet- and Na-type, commonly exist in all 3 strains of mice. The most clear strain difference was found in the sensitivity to D-phenylalanine, which produced good responses in 'sweet-type' fibers of C57BL mice but not in those of C3H and BALB mice. This suggests the possibility that D-phenylalanine has a taste to C57BL mice that is similar to that of sucrose and that it tastes different to C3H and BALB mice.  相似文献
10.
C57BL/6 and DBA/2 were compared in the 5-choice serial reaction time task for differences in performance related to attention and impulsivity. The goal was to examine behavioural processes in mice that may relate to ADHD in humans. Groups of male mice were trained to nose-poke in response to a stimulus light presented randomly in one of five holes; correct responses were reinforced with food. During training the stimulus duration (SD) was reduced progressively from 60 to 0.5 s. The C57BL/6 and DBA/2 mice did not differ during early stages of training when attentional demands were low (SD of 60, 10 or 5 s). As task demands increased, strain differences emerged; C57BL/6 mice were more accurate than DBA/2 mice with stimuli of 2, 1 and 0.5 s. DBA/2 mice also made more anticipatory (impulsive) responses during inter-trial intervals than C57BL/6 mice at SD of 5, 2, 1 and 0.5 s. The ability to carry out the task was present in both strains of mice but they differed significantly in the levels of performance that were achieved. It is argued that the differences in accuracy and anticipatory responding were closely related and that the primary difference between the strains may be in impulsivity.  相似文献
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