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1.
In order to analyze the epileptogenic mechanisms of caffaine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A1 adenosine receptor subtype. The A1 receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occuring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts.  相似文献   
2.
The xanthine, hypoxanthine, and total oxypurine levels were determined in the CSF of 28 hydrocephalic patients (age from newborn to 2 years) and 8 healthy controls using HPLC. The Evans' index, the mean weekly increase in cranial circumference, and the intracranial pressure were also measured. Of the hydrocephalic patients 13 were self-compensated and the other 15 had a shunt implanted during the course of the study. The mean xanthine, hypoxanthine, and total oxypurine levels in the normal children were 5.20, 5.94, and 11.29 mol/l, respectively. In the self-compensated hydrocephalics these levels were 5.17, 5.71, and 10.79 mol/l, respectively. In the noncompensated hydrocephalics, they were 9.90, 9.91, and 19.82 mol/l. The differences between the latter group and the first two are statistically significant (P<0.001). The mean Evans' index and the mean weakly increase in cranial circumference in the self-compensated hydrocephalics were 0.35 and 0.25 cm, respectively. In the noncompensated hydrocephalics, they were 0.55 and 0.95 cm. The differences between the two groups are statistically significant (P<0.001). Two weeks after implantation of shunts in the noncompensated cases, the mean xanthine, hypoxanthine, and total oxypurine levels fell to 4.22, 4.57, and 8.80 mol/l, respectively. These changes are statistically significant (P<0.001). We think that the two criteria (clinical and biochemical) are equally useful for the prediction of self-compensation in hydrocephalic children and that the oxypurine values after shunt implantation can be used to monitor progress in noncompensated cases.  相似文献   
3.
The free radical-generating system of xanthine and xanthine oxidase is commonly used experimentally as a source of superoxide anion, which can produce oxidative stress, leading to cellular damage and death. Models of oxidative stress are important in elucidating pathologies associated with increased levels of reactive oxygen species, including stroke and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. We therefore, examined the effect of the xanthine/xanthine oxidase system on the viability of postnatal cerebellar granule neurones obtained from 8-day old Sprague–Dawley rat pups. Xanthine (100 μM) and xanthine oxidase (0.02 U/ml) applied for 1 or 6 h reduced the viability of cells at 8 div assessed using the alamar blue assay, and induced morphological changes, such as shrinkage of the cell bodies and neurites. Heat-inactivation of xanthine oxidase resulted in complete loss of its activity. Superoxide dismutase (250 U/ml) failed to modify the damage by xanthine and xanthine oxidase, while catalase (250 U/ml) completely prevented it. When applied alone, xanthine oxidase significantly lowered cell viability, an effect that was blocked by allopurinol and catalase, but not by superoxide dismutase. The results indicate that xanthine and xanthine oxidase can produce predominantly hydrogen peroxide instead of the superoxide anion. Cerebellar granule cells in culture may also possess significant levels of endogenous xanthine.  相似文献   
4.
别嘌呤醇对离体大鼠缺血再灌注心肌的保护作用   总被引:2,自引:0,他引:2  
为探讨别嘌呤醇(allo)对心肌的保护作用与机理,采用离体大鼠心脏灌注模型,研究allo对缺血再灌注心肌的保护作用。结果表明心肌缺血再灌注后磷酸肌酸肌酶(CPK)释放增多,超氧化物歧化酶(SOD)活性降低,黄嘌呤氧化酶(XO)活性和丙二醛(MDA)量增加,心肌超微结构破坏明显。allo通过抑制氧自由基的生成对缺血再灌注心肌起保护作用。  相似文献   
5.
We have examined the potency of several adenosine receptor antagonists at adenosine A1 and A2A receptors using quantitative autoradiography and have compared the results with those of previous studies using the same radioligands in membrane preparations. The agonists [3H]cyclohexyladenosine and [3H]2-[p-(2-carbonylethyl)-phenylethylamino]-5′-N-ethylcarboxamido adenosine ([3H]CGS 21680) were used as radioligands for the two receptors. The results show that 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) is almost 1000-fold and 8-chloro-4-cyclohexyl-amino-1-(trifluoromethyl)[1,2,4]triazolo[4,3-a] quinoxaline (CP-68,247) about 300-fold more potent at adenosine A1 receptors in cortex and striatum than at striatal adenosine A2A receptors. Conversely, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine (SCH 58261) is approximately 1000-fold and 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM 241,385) about 400-fold more potent at adenosine A2A than at A1 receptors. Caffeine and its metabolites did not show any selectivity. Other studied antagonists were non-selective or showed a modest (20- to 40-fold) adenosine A2A receptor selectivity. Thus, only a few of the antagonists show such high selectivity that it is not offset by differences in drug distribution and levels of receptor subtype expression.  相似文献   
6.
Summary The lipolytic and hyperglycaemic actions of three xanthine derivatives of dopamine were studied in fed rats by determining the plasma levels of glycerol, free fatty acids and glucose. All three derivatives, 7-propyl-theophylline-dopamine, 7-(3-methyl)-propyl-theophylline-dopamine and 7-(2-methyl)-propyl-theophilline-dopamine, had a longer duration of action on lipolysis than had dopamine. These xanthine derivatives stimulated lipolysis at 10-to 100-times lower doses than dopamine and also had a greater maximal effect. Glycogenolysis was stimulated by 7-(3-methyl)- and 7-(2-methyl)-propyl-theophyllinedopamine at lower doses than by dopamine, the maximal effect, however, being smaller than that of dopamine. 7-propyl-theophylline-dopamine had practically no hyperglycaemic effect. Pretreatment with the -adrenoceptor blocking agents, phentolamine and dihydroergotamine, blocked the increase of the plasma level of glucose induced by dopamine, whereas the hyperglycaemic effect of 7-(3-methyl)-propyl-theophylline-dopamine was better antagonized by the -adrenoceptor blocking agent, propranolol. The -adrenoceptor antagonists had no clearcut effects on the lipolytic action of dopamine or its xanthine derivatives, which was, however, clearly antagonized by pretreatment with propranolol. Desipramine and reserpine, at doses which prevented the metabolic actions of tyramine, partially blocked the lipolytic and hyperglycaemic effect of dopamine, but not those of the xanthine derivatives. This suggests that the xanthine derivatives- in contrast to dopamine- do not have an indirect, tyramine-like component in their metabolic actions. Pretreatment with pargyline, an inhibitor of monoamine oxidase, strongly enhanced the metabolic effects of dopamine, but to a lesser extent the actions of its xanthine derivatives, indicating that these derivatives are more resistant to monoamine oxidase than is dopamine. The results indicate that the xanthine derivatives have metabolic effects similar to those of dopamine, but differ from dopamine in their activity and relative affinity with respect to metabolic - and -adrenoceptors and in their mechanism of action as well as in their metabolism.Deceased August 6, 1978  相似文献   
7.
NFAT5 (nuclear factor of activated T cells), a well‐known osmoprotective factor, can be activated by isotonic stimuli such as Toll‐like receptor (TLR) triggering. However, it is unclear how NFAT5 discriminates between isotonic and hypertonic stimuli to produce different functional and molecular outcomes. Here, we identified a novel XO–ROS–p38 MAPK–NFAT5 pathway (XO is xanthine oxidase, ROS is reactive oxygen species) that is activated in RAW 264.7 macrophages upon isotonic TLR stimulation. Unlike what is seen under hypertonic conditions, XO‐derived ROS were selectively required for the TLR‐induced NFAT5 activation and NFAT5 binding to the IL‐6 promoter in RAW 264.7 macrophages under isotonic conditions. In mouse peritoneal macrophages and human macrophages, TLR ligation also induced NFAT5 activation, which was dependent on XO and p38 kinase. The involvement of XO in NFAT5 activation by TLR was confirmed in RAW 264.7 macrophages implanted in BALB/c mice. Moreover, allopurinol, an XO inhibitor, suppressed arthritis severity and decreased the expression of NFAT5 and IL‐6 in splenic macrophages in C57BL/6 mice. Collectively, these data support a novel function of the XO–NFAT5 axis in macrophage activation and TLR‐induced arthritis, and suggest that XO inhibitor(s) could serve as a therapeutic agent for chronic inflammatory arthritis.  相似文献   
8.
Objective:To evaluate in vitro antioxidant and apoptotic activities of Crperus rotundas(C.rotundus).Methods:The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C.rotundus aerial part were determined.In addition,these extracts were also investigated for their cytotoxic and apoptotic activities.The major compound of the methanol extract was isolated.Both metlianol and aqueous extracts(300,150,and 50μg/mL)were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system.However,16,8,and 4 mg/mL of each extract were tested to investigate their OH.formation scavenging potential.Aqueous extract(800,400.and 200μg/mL)and melhunol extract(350,175,and 88μg/mL)were tested against lipid peroxidation,induced by 75μM H_2O_2,The cytotoxicity(by MTT assay)and cell DNA fragmentation of both extracts were evaluated Inwards K562 and L1210 cell lines.The major compound was obtained from the butanol fraction of methanol extract and its structure was determined by KMN spectroscopic analysis.Results:The methanol and aqueous extracts showed respectively,88%and 19%inhibition of xanthine oxidase activity.Vet.the same extracts inhibited lipid peroxidation by 61.5%and 42.0%.respectively.Roth extracts inhibited OH.formation by 27.1%and 25.3%,respectively.Only methanol cxtract induced DNA degradation.Orientin was determined as the major compound isolated from the butanol fraction of metlianol extract.Conclusions:It appears that C.rotundus extracts exhibit a potential use as a natural antioxidant and an apoptosis inducer.  相似文献   
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