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21.
We describe a system we developed that enabled simultaneous measurements of either epithelial calcium ion concentration ([Ca2+]i) or sodium ion concentration [Na+]i with the ciliary beat frequency (CBF) in native ciliated epithelia using either Fura-2 (AM) or SBFI (AM) ratiometric fluorescence photon counting along with nonstationary laser light scattering. Studies were performed using native epithelial tissues obtained from ovine tracheae. The dynamic range of the laser light-scattering system was determined by a simulated light beating experiment. The nonstationary CBF was demonstrated by the time-frequency analysis of the raw photon count sequences of backscattered heterodyne photons from cultured and native epithelia. Calibrations of calcium and sodium ion concentrations were performed using the respective Fura-2 and SBFI impermanent salts as well as in native epithelia. The cumulative responses of 10–6, 10–5, and 10–4} M nifedipine on [Ca2+]i together with the CBF as well as the cumulative responses of 10–5, 10–4, and 10–3 M amiloride on [Na+]i together with the CBF were also determined. Nifedipine decreased [Ca2+]i but had no effect on CBF. Amiloride decreased [Na+]i and CBF. Stimulation of CBF corresponded with either an increase of [Na+]i or an increase of [Ca2+]i. Decreases of [Na+]i or substantial decreases of [Ca2+]i were associated with decreases in the CBF. These data demonstrate the utility of this system for investigating the regulatory mechanisms of intracellular ions dynamics and the CBF in native epithelia. © 1998 Biomedical Engineering Society.
PAC98: 8780+s, 8722-q, 4262Be 相似文献
22.
Carlo Alberto Maggi Sandro Giuliani Paolo Santicioli 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(5):510-522
We have investigated the effect of the dihydropyridine calcium channel agonist, Bay K 8644, and of the plant alkaloid blocker of calcium-induced calcium release (CICR) from the sarcoplasmic reticulum, ryanodine, on the refractory period, action potential and mechanical response of the guinea-pig isolated ureter to electrical stimulation. All experiments were performed in ureters pre-exposed to 10 M capsaicin to eliminate the inhibitory influence exerted by local release of sensory neuropeptides on ureteral excitability and contraction. In organ bath experiments, electrical field stimulation with parameters which produce direct excitation of ureteral smooth muscle (train of pulses at 10 Hz, 5 ms pulse width, 60 V for 1 s) produced tetrodotoxin- (1 M) resistant phasic contractions. The response to EFS was abolished by nifedipine (1 nM-3 M) and was enhanced by Bay K 8644 (1 nM-3 M). In the presence of Bay K 8644 (1 M), nifedipine (30 M) abolished the evoked contractions. Ryanodine (10–100 M) had no significant effect on the amplitude of evoked contraction. The response of the guinea-pig ureter to direct electrical stimulation of smooth muscle is characterized by a refractory period: at least 40 s interstimulus interval was required to produce a second response in all preparations tested. Bay K 8644 (1 M) markedly reduced the refractory period of the ureter and a similar effect was observed with ryanodine (100 M). To further analyze the effect of Bay K 8644 and ryanodine on the refractory period, the response of the ureter was investigated over a 10 s period of stimulation (other parameters as above). In control ureters, continuous stimulation for 10 s produced only one phasic contraction just after the beginning of the train of stimuli. In the presence of Bay K 8644 or ryanodine, more than one phasic contraction developed during a 10 s stimulation, i.e. the refractory period became shorter than the train duration. When both Bay K 8644 and ryanodine were tested on the same preparations, an additive excitatory effect was observed on the mechanical response to electrical stimulation. A slight elevation of KCI concentration (5–10 mM) reduced the refractory period of the ureter as observed with ryanodine or Bay K 8644. Application of KCI (80 mM) produced a biphasic contractile response of the ureter: a series of phasic contractions occurred first, which were then replaced by a slowly developing tonic response. Bay K 8644 (1 M) enhanced both components of the response to KCI. Ryanodine (10 and 100 M) markedly prolonged the duration of phasic contractions evoked by KCI and, at 100 M, slightly (about 25%) reduced the amplitude of tonic contraction.In sucrose gap experiments, electrical stimulation (single pulse, 40–130 V, 1–3 ms pulse duration) evoked an action potential and accompanying phasic contraction which were abolished by 1 M, nifedipine. Bay K 8644 (1 M) produced a marked prolongation of action potential duration, increased the number of spikes and enhanced contraction amplitude and duration. Ryanodine (100 M) depolarized the membrane, reduced the delay between stimulus application and onset of the action potential, shortened the action potential at 50% of repolarization and increased afterhyperpolarization, without producing marked effects on the accompanying mechanical response. KCI (5 mM) likewise produced a slight membrane depolarization and decreased latency between stimulus application and onset of the action potential but did not affect action potential duration. The combined administration of ryanodine and Bay K 8644 produced additive effects on action potential and contractions: furthermore, the contractile phase of the overall contraction-relaxation cycle was significantly prolonged by the combined administration of the two agents, an effect not observed with either drug alone. In the presence of both Bay K 8644 and ryanodine, multiple action potentials and contractions were observed during a train of pulses delivered at a frequency of 1 Hz for 12 s: when a second action potential was triggered before relaxation of the preceding contraction, a summation of the contractile response was observed. These findings demonstrate that availability of voltage-dependent L-type calcium channels is a major mechanism in determining the refractory period of the guinea-pig ureter and, consequently, can be considered as a limiting step in regulating the maximal frequency of ureteral peristalsis. Furthermore, a ryanodine-sensitive mechanism regulates the excitability and contraction-relaxation cycle of ureteral smooth muscle. The increased electrical excitability of the ureter observed in the presence of ryanodine may involve blockade of transient outward currents triggered by spontaneous calcium release from the store and consequent membrane depolarization. 相似文献
23.
The dissolution behaviour of a direct compression compact prepared with sodium diclofenac and dibasic calcium phosphate (DCP) in different weight ratios with or without Biosoluble polymer® (acrylic-based resin) was investigated in distilled water and in a medium with changing pH. The results indicate that the amount of sodium diclofenac released from the compact was dependent on the amount of drug and DCP used in the compact, and was also controlled by the amount of Biosoluble polymer® added. A chemical reaction forming diclofenac acid might occur on the surface of the sodium diclofenac compact during exposure to the acidic medium, which was confirmed by diffuse-reflectance spectroscopy. The tablet with a 12 weight ratio of sodium diclofenac to DCP exhibited a sustained-release behaviour, similar to commercial sustained-release products (Voltaren SR-100® and Grofenac Retard®), but a lower release rate was found as compared to the commercial products. The dissolution behaviour of the study tablet and the commercial products was found to be dependent on the dissolution medium and the rotating speeds. Glass beads were added to the dissolution assembly to simulate the influence of food, and the enhanced friction between tablet and glass beads might result in a higher dissolution rate of the tablet and the commercial products. 相似文献
24.
Else Müller-Schweinitzer 《Naunyn-Schmiedeberg's archives of pharmacology》1983,324(1):64-69
Summary The influence of the calcium antagonist nifedipine on 1- and 1-adrenoceptor vasoconstrictor effects was investigated in vitro. Changes in tension were monitored isometrically on helical strips of canine circumflex coronary and saphenous arteries suspended in 10 ml organ baths and of saphenous veins superfused with Krebs-Henseleit solution. Distinction between 1- and 2-adrenoceptor was made by using selective -adrenoceptor blocking drugs such as rauwolscine, yohimbine, corynanthine and prazosin, and the agonists noradrenaline, phenylephrine and guanfacine. In venous and both arterial vascular smooth muscles, the contractile process could be triggered by stimulation of both 1- and 2-like adrenoceptors. Nifedipine inhibited the venoconstrictor response to the 2-agonist guanfacine, leaving that to the 1-agonist phenylephrine unchanged. In saphenous arteries, nifedipine in addition to guanfacine also antagonized constrictor responses to phenylephrine, though to a significantly weaker extent. In circumflex coronary arteries, nifedipine was equally potent in antagonizing responses to both 1- and 2-adrenoceptor stimulation.It is suggested that the susceptibility of -adrenoceptormediated vasoconstrictor effects to blockade by calcium antagonists depends not only on the subtype of -adrenoceptor but, in addition, on the type and origin of vascular smooth muscle and may be a reflection of tissue variations in intracellular calcium stores. 相似文献
25.
S. Jost W. Rafflenbeul J. Deckers B. Wiese H. Hecker P. Nikutta P. Lippolt P. Lichtlen 《European journal of epidemiology》1992,8(Z1):107-119
Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers.INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CHAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). 相似文献
26.
B. G. Woodcock P. A. Thürmann S. Pfleiderer N. Reifart 《European journal of clinical pharmacology》1992,43(6):587-590
Summary The ability of a fatty-alcohol matrix, slow-release tablet of nifedipine 60 mg to maintain a 24-hour antiischaemic action in the fixed dose of 60 mg once daily has been investigated in a randomised, placebo-controlled, double-blind trial.12 normotensive patients with angiographically proven coronary artery disease (stenosis of at least one major vessel 70%) were studied. The anti-ischaemic response was assessed over a period of 4 days as changes in the exercise-induced ST-segment depression 6 h and 24 h postdose, and ST segment changes in 24-h ambulatory ECGs.A measurable anti-ischaemic response was observed in 8 of the 12 patients. Exercise-induced ST-segment depression 6 h after the administration of nifedipine was reduced by 30% compared to placebo, and there was still a measurable anti-ischaemic response 24-h post-dosing. Both responses were independent of changes in exercise blood pressure. In 7 patients with ischaemic episodes in the 24-h ECGs, nifedipine treatment had only a minor effect on the intensity and duration of ischaemia.It is concluded that a significant anti-ischaemic effect lasting 24 h could be demonstrated using effort-induced ST-segment changes in patients with angiographically proven coronary heart disease, who were treated once daily with nifedipine 60 mg as a fatty-alcohol slow release tablet. 相似文献
27.
Twenty-four male volunteers were given obidoxime tablets in quantities ranging from 1.84–3.58 g in a single dose, or 7.36 g divided into 4 equal doses. With the lowest dose, average peak plasma level of the drug was 1.9 g/ml and after the highest single dose it was 5.6 g/ml, both attained 1.5 h after administration. In the multiple-dosed individuals, plasma levels of the oxime increased gradually following each additional dose, reaching a peak of 3.5 g/ml after the last dose.Thirteen individuals complained of one or more of the following side effects: pallor, nausea, pyrosis, headache, generalized weakness, sore throat, and paresthesia of the face muscles.Activities of blood cholinesterase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, as well as hematocrit values, heart rate, and blood pressure were not affected.It is postulated that due to the undesirable side effects, the general use of obidoxime tablets should not be recommended. However, prophylactic oral treatment with obidoxime could be considered for persons at high risk of organophosphate poisoning or when parenteral administration might not be feasible. 相似文献
28.
目的:考察清火解毒片的药理作用。方法:采用体内外抑菌法、毛细血管通透性法、鼠耳肿胀法、发热反应法、氨雾致咳法、醋酸刺激扭体法。结果:该药对常见的呼吸道感染小鼠有保护作用趋势;对醋酸所致小鼠腹腔毛细血管通透性亢进有明显抑制作用,但对巴豆油所致的小鼠耳肿胀的抑制作用不明显;对2,4-二硝基苯酚致热大鼠的解热作用也不明显;能明显延长氨雾诱发小鼠咳嗽反应潜伏期、减少咳嗽次数;还能明显抑制醋酸所致小鼠的扭体反应。结论:该药具有一定的抗菌、抗炎、镇咳、镇痛作用。 相似文献
29.
藏药晶珠虫草含片质量标准研究 总被引:5,自引:0,他引:5
目的:建立晶珠虫草含片(冬虫夏草,红景天、黄芪、青果、人参、麦冬等)的质量标准。方法:采用TLC法对处方中人参、麦冬进行鉴别;用薄层描法测定黄芪甲苷的含量。结果:在TLC色薄中检出人参、麦冬;黄芪甲苷在0.5-2.5uL范围内呈良好的线性关系,r=0.9999,平均回收率98%。RSD为1.35。结论:所建立的方法简单可行,重现性好,为晶珠虫草含片质量控制提供了方法。 相似文献
30.