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1.
A. U. Ziganshin J. Yu. Falou V. A. Mamedov L. V. Mustakimova 《Pharmaceutical Chemistry Journal》2005,39(6):303-307
The ability of 12 new thiazole derivatives to influence the muscle contractility mediated by purine P2X receptors has been
studied in vitro using isolated tissues of rats and guinea pigs. Most of the synthesized compounds did not cause significant effects, but
two compounds exhibited pronounced antagonism with respect to P2X-mediated contractility response. These compounds offer a
good starting point for the synthesis of new effective antagonists of P2 receptors.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 22 – 25, June, 2005. 相似文献
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L. E. Ziganshina A. U. Ziganshin C. H. V. Hoyle G. Burnstock 《Inflammation research》1996,45(2):96-102
ATP-induced inflammation was investigated using subplantar injection in the mouse hind paw. The order of efficacy of purinoceptor agonists for inducing paw oedema (30 nmol per paw) was ATP=,-methylene ATP=2-methylthio ATP > adenosine > UTP > ADP > AMP. Diadenosine polyphosphates effectively induced paw oedema formation with an order of efficacy of: P1, P4-di(adenosine-5)tetraphosphate =P1,P5-di(adenosine-5)-pentaphosphate= P1,P6-di(adenosine-5) hexaphosphate ATP=P1,P3-di(adenosine-5)triphosphate > P1,P2-di(adenosine-5)pyrophosphate. Systemic administration of P2-purinoceptor antagonists (30–100 mol/kg), suramin, 4,4-diisothiocyanatostilbene-2,2-disulphonate, pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid and cibacron blue, reduced the intensity of ATP-induced oedema. At 30 mol/kg 8-(p-sulfophenyl)theophylline (non-selective adenosine receptor antagonist), 3,7-dimethyl-1,1-propargyl-xanthine (adenosine A2 receptor antagonist), triprolidine (histamine H1 receptor antagonist), ranitidine (histamine H2 receptor antagonist) and ketanserin (5-hydroxytryptamine 5-HT2 receptor antagonist), but neither 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist), nor indomethacin (cyclooxygenase inhibitor) inhibited the ATP-induced swelling. Topical (100 nmol per paw), but not systemic (100 mol/kg) administration of NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) reduced the intensity of the ATP-induced paw oedema. These results show that ATP can induce an inflammatory oedematous reaction and contribute to our understanding of the underlying mechanisms.accepted by G. Bowen 相似文献
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Ziganshin AU Zaitsev AP Shamsutdinov AF 《Bulletin of experimental biology and medicine》2002,133(3):255-257
We studied contractile responses of isolated smooth muscles from human uterus induced by P2 receptor agonists. In preparations from pregnant uterus all tested P2 receptor agonists caused smooth muscle contractions. The relative activity of P2 receptor agonists decreased in the following order: a,b-methylene-ATP-uridine triphosphate-ATP. Responses induced by ATP and ADP were similar. The amplitude of contractions induced by alpha,beta-methylene-ATP significantly decreased in the presence of P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. None of tested P2 receptor agonists induced contractions of isolated myometrium from nonpregnant women. Our results indicate that pregnant human uterus contains P2 receptors mediating the contractile response. 相似文献
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Zenchenko KI Kokoz YM Ivanov VT Ziganshin RK Vinogradova OS 《Neuroscience and behavioral physiology》2001,31(4):395-403
Evoked neuron activity in slices of the medial septal area and its modulation by neuropeptides and monoamines was studied in two groups of ground squirrels – hibernating and awake animals. Electrical stimulation of the medial forebrain bundle evoked predominantly inhibitory effects of different durations. In addition, responses were seen consisting of resetting of the phase of background volleys to the stimulus after initial inhibition; there were also small numbers of short-latency single-spike responses. All the neuropeptides tested, which had been identified from the brains of hibernating animals, induced differentiated reversible effects consisting of modulation of responses; changes in evoked activity were seen significantly more often than shifts in spontaneous activity. The effects depended on the state of the animal. Thus, peptide TSKYR increased the duration of inhibition in hibernating ground squirrels but shortened inhibition in awake animals. Peptide TSKY, which had little effect in hibernating animals, increased the duration of inhibition in awake animals. Dipeptide DY, which decreased the duration of inhibition and increased the amplitude of the activatory components of responses in hibernating ground squirrels, had little effect in awake animals. The effects of noradrenaline and serotonin correlated to a large extent with their effects on spontaneous activity. It is suggested that endogenous substances are involved in creating the conditions required for increasing the latent excitability and reactivity of septal neurons during hibernation. This allows the medial septal area to function as a sentry post, allowing the receipt of signals and urgent arousal during hibernation. 相似文献
6.
Ziganshin AU Rychkov AV Ziganshina LE 《Bulletin of experimental biology and medicine》2000,130(10):961-963
In vitro experiments showed that P2X-receptor agonist ,-methylene-ATP and electrical field stimulation in the presence of muscarinic and -adrenoreceptors blockers induced contractile responses of isolated guinea pig bladder, which were more pronounced at 30°C than at 37°C or 42°C. P2X-receptor antagonist pyridoxal-6-phosphate-2',4'-disulfonic acid, produced a more potent inhibitory effect on contractions induced by electrical field stimulation at 30°C in comparison with that at 37°C or 42°C, while the contractions induced by ,-methylene-ATP were similarly suppressed at all examined temperatures. 相似文献
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Glycol ethers such as ethylene glycol monomethyl ether (EGME)are common solvents used in many industrial products. A largenumber of individuals are exposed to EGME through differentexposure routes. We investigated the differential distributionof EGME following various routes of administration using wholebody autoradiographic (WBA) techniques. Male B6C3F1 mice weretreated with tracer iv or oral doses of [2-14C]EGME.(4.05 µgEGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24hr following treatment. In both groups of animals the highestlevels of radioactivity were detected in the liver, urinarybladder, bone marrow, kidney, and epididymis, at 1- and 24-hrtime periods. Computer-assisted quantitation of WBA indicatedthat there was markedly higher deposition of [2-14 and/or itsmetabolites in various tissues of the orally treated animalsthan in animals treated intravenously. Our studies also suggestthat [2-14C]EGME is rapidly distributed either from blood orstomach to various tissues. Preferential deposition of radioactivityin the peripheral tissues of the bone, with a progressive inwardaccumulation in the bone marrow, was observed. Selective permeabilityof EGME and/or its metabolites was indicated by the higher uptakeby the epididymis than that by testis. The high levels of radioactivityin biosynthetically active tissues, e.g., the liver, bone marrow,and gastric mucosa, is an indication of persistent interactionof the compound with cellular components of these tissues. Theseinteractions may lead to EGME toxicity. 相似文献
10.
Mohammad A. Zafar Julia Fayanne Chen Jinlin Wu Yupeng Li Dimitra Papanikolaou Mohamed Abdelbaky Thais Faggion Vinholo John A. Rizzo Bulat A. Ziganshin Sandip K. Mukherjee John A. Elefteriades 《The Journal of thoracic and cardiovascular surgery》2021,161(2):498-511.e1
ObjectivesElucidating critical aortic diameters at which natural complications (rupture, dissection, and death) occur is of paramount importance to guide timely surgical intervention. Natural history knowledge for descending thoracic and thoracoabdominal aortic aneurysms is sparse. Our small early studies recommended repairing descending thoracic and thoracoabdominal aortic aneurysms before a critical diameter of 7.0 cm. We focus exclusively on a large number of descending thoracic and thoracoabdominal aortic aneurysms followed over time, enabling a more detailed analysis with greater granularity across aortic sizes.MethodsAortic diameters and long-term complications of 907 patients with descending thoracic and thoracoabdominal aortic aneurysms were reviewed. Growth rates (instrumental variables approach), yearly complication rates, 5-year event-free survival (Kaplan–Meier), and risk of complications as a function of aortic height index (aortic diameter [centimeters]/height [meters]) (competing-risks regression) were calculated.ResultsEstimated mean growth rate of descending thoracic and thoracoabdominal aortic aneurysms was 0.19 cm/year, increasing with increasing aortic size. Median size at acute type B dissection was 4.1 cm. Some 80% of dissections occurred below 5 cm, whereas 93% of ruptures occurred above 5 cm. Descending thoracic and thoracoabdominal aortic aneurysm diameter 6 cm or greater was associated with a 19% yearly rate of rupture, dissection, or death. Five-year complication-free survival progressively decreased with increasing aortic height index. Hazard of complications showed a 6-fold increase at an aortic height index of 4.2 or greater compared with an aortic height index of 3.0 to 3.5 (P < .05). The probability of fatal complications (aortic rupture or death) increased sharply at 2 hinge points: 6.0 and 6.5 cm.ConclusionsAcute type B dissections occur frequently at small aortic sizes; thus, prophylactic size-based surgery may not afford a means for dissection protection. However, fatal complications increase dramatically at 6.0 cm, suggesting that preemptive intervention before that criterion can save lives. 相似文献