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101.
The 125I-labeled sulfated cholecystokinin (CCK) analogue, [D-Tyr25,Nle28,31]CCK-(25-33), bound saturably to membranes from rat cerebral cortex and to brain tissue sections. Competition studies suggested binding to sites of the CCKB subtypes. The high affinity for brain membranes (Kd = 0.14 nM) and high specific binding to brain sections (80-90% specific binding), as well as its high specific radioactivity, makes it a suitable ligand for autoradiographic studies of cholecystokinin receptors. 相似文献
102.
The kinetic and pharmacological characteristics of the binding of the oxazoline antihypertensive drug, [3H]rilmenidine, to membranes of rat cerebral cortex have been determined. Computerised resolution of curvi-linear, equilibrium binding isotherms was consistent with the existence of two distinct binding sites for [3H]rilmenidine: Kd 17.3 +/- 7.41 nM, Bmax 0.197 +/- 0.06 pmol/mg protein and Kd 254 +/- 48 nM, Bmax 1.59 +/- 0.08 pmol/mg protein. Moreover, the resolution of two association and dissociation rates also suggested the existence of two binding site populations. Drug inhibition studies revealed that specific binding of [3H]rilmenidine (2 nM) was only inhibited by a maximum of 50% by the catecholamines, adrenaline and noradrenaline, but was completely inhibited by some oxazolines, by guanabenz (a guanidino drug) and by several imidazoline compounds including naphazoline, oxymetazoline and clonidine. Binding isotherms for these drugs were also best fit by a two-site model. The relative Ki values at the high affinity site for [3H]rilmenidine and the number of these high affinity sites are consistent with this site being an alpha 2-adrenoceptor. The high affinity of oxymetazoline and low affinity of prazosin for high affinity [3H]rilmenidine binding sites together with the rank order of potency of oxymetazoline greater than phentolamine greater than SKF 104078 greater than ARC-239 greater than prazosin suggest that [3H]rilmenidine binds to the alpha 2A sub-type of adrenoceptor. Computer-resolved Ki values for drugs at the larger number of lower affinity binding sites were very similar to Ki values determined in the presence of 10 microM adrenaline (used to block alpha 2-adrenoceptor binding).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
103.
The development of tolerance to the anticonvulsant effects of clonazepam, but not sodium valproate, in the amygdaloid kindled rat 总被引:3,自引:0,他引:3
The effects of chronic treatment with clonazepam and sodium valproate were studied on kindled amygdaloid seizures in rats. Fully kindled rats were given an intraperitoneal (i.p.) injection of either vehicle (1.0 ml/kg), clonazepam (0.3 mg/kg) or sodium valproate (200 mg/kg) twice daily for 12 days. Each rat was stimulated through an amygdaloid electrode 30 min after the morning dose. While both drugs initially blocked and kindled seizure (P less than 0.01), the results showed a significant trend (P less than 0.02) in the development of tolerance to the anticonvulsant action of clonazepam but no significant tolerance to the action of valproate. 相似文献
104.
α-Methyldopa administration to rats (200mg kg?1 s.c.) produced a marked reduction in levels of noradrenaline and dopamine in anterior hypothalamic-preoptic nuclei implicated in catecholamine-mediated cardiovascular-inhibitory functions. Similar effects were observed in medullary nuclei, including the n. tractus solitarius which has been postulated as a site for the hypotensive action of α-methyldopa. The metabolite, α-methyldopamine, accumulated rapidly and 4hr after drug administration levels were higher in most nuclei than in either the medulla oblongata or hypothalamus as a whole, suggesting greater uptake of α-methyldopa into these specific areas. This was also reflected by higher levels of α-methylnoradrenaline in the nuclei than in the gross regions. The time course of accumulation and disappearance of α-methylnoradrenaline in the n. tractus solitarius differed from that in the anterior hypothalamic-preoptic nuclei and more closely correlated with the reported time course of the hypotensive effect of α-methyldopa. However, the action of this metabolite in both areas may contribute to the fall in blood pressure. 相似文献
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107.
Jarrott SE Zarit SH Stephens MA Townsend A Greene R 《American journal of Alzheimer's disease and other dementias》2005,20(3):181-190
Family caregivers of persons with dementia rely on a range of resources to provide care and cope with caregiving stressors. Informal (unpaid) and formal (paid) instrumental support contribute to diverse caregiver outcomes. Previous research of caregiver support has focused on subjective measures of help or has compared caregivers receiving formal services to those who do not. We focused instead on the effects of change in the amount of formal and informal instrumental assistance on caregivers' distress. We expected that greater gains in assistance would be associated with greater reduction of caregivers' distress. Increases informal but not informal levels of assistance were associated with improvement in each measure of distress. Additional measures may be needed to fully understand the effects of informal and formal assistance. 相似文献
108.
A novel, rapid, computerized method for quantitation of neuronal damage in a rat model of stroke 总被引:3,自引:0,他引:3
Callaway JK Knight MJ Watkins DJ Beart PM Jarrott B Delaney PM 《Journal of neuroscience methods》2000,102(1):53-60
Determination of extent of infarction in animal models of cerebral ischemia is most commonly achieved by either classical histology (thionin staining) and light microscopy or staining with 2,3, 5-triphenyltetrazolium chloride (TTC). These techniques have limitations and we now describe a novel technique and its validation for assessment of the neuroprotective activity of AM-36, a novel arylalkypiperazine compound with combined antioxidant and sodium channel blocking activity. AM-36 (1.8 mg/kg i.p.) or vehicle, was administered 30 min, 24 and 48 h after endothelin-1-induced middle cerebral artery occlusion in conscious rats. Rats were killed at 72 h, brains removed and frozen in liquid nitrogen prior to coronal sectioning. Using a simple apparatus relying on basic principles of light propagation and a computerised image analysis system, ischemic damage in unstained slide-mounted sections was clearly visualised and measured. AM-36 significantly reduced the area of infarct in both cortex and striatum. The method was verified by thionin staining, and light microscopy. Linear regression analysis showed a highly significant correlation between methods at 72 h for infarct area in the cortex and striatum. Highly significant correlations between methods were found at 3 and 24 h after ischemia. Our method quickly and clearly delineates areas of damage in a manner superior to conventional staining methods. 相似文献
109.
S N Anavekar L G Howes B Jarrott M Syrjanen E L Conway W J Louis 《Journal of clinical pharmacology》1989,29(4):321-326
Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml were achieved after 3.6 +/- 1.2 hours. After 5 days of repetitive dosing the maximal concentration was significantly higher, 0.66 +/- 0.06 ng/ml and remained so throughout chronic therapy (P = 0.018). The AUC, Tmax and T1/2 did not differ significantly between the acute dose and the chronic dosing pharmacokinetic studies. Clonidine also produced a significant fall in blood pressure. Supine diastolic blood pressure fell from 106 +/- 5 mmHg predose to 99 +/- 6 mmHg 2 hours after the first dose (P less than 0.05). The corresponding values after cyclopenthiazide alone were 108 +/- 8 and 105 +/- 8 mmHg (P = 0.13). Similar falls in blood pressure were produced during chronic therapy. 相似文献
110.
Gaugler JE Jarrott SE Zarit SH Stephens MA Townsend A Greene R 《International journal of geriatric psychiatry》2003,18(1):55-62
BACKGROUND: The objective of this study was to determine whether adult day service use interacts with decreases in primary caregiving hours (i.e. the time caregivers spent on activities of daily living/instrumental activities of daily living, memory problems, and behavior problems for patients) to alleviate caregiver stress and negative mental health over time. METHODS: Three-month longitudinal data from the Adult Day Care Collaborative Study (n=400) were used. RESULTS: Decreases in memory problem hours among adult day service users were associated with reduced feelings of role overload; decreases in ADL hours among non-users were associated with decreases in worry and strain over a three-month period. CONCLUSION: The findings suggest that adult day services are potentially effective in restructuring caregiving time and providing respite to family members. 相似文献