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31.
Lemmer Björn Winkler Horst Ohm Thomas Fink Markus 《Naunyn-Schmiedeberg's archives of pharmacology》1985,330(1):42-49
Summary Comparative pharmacokinetic studies with the -receptor blocking drugs propranolol, metoprolol, sotalol and atenolol, differing greatly in lipophilicity, and their main route of elimination were performed in light-dark-synchronized rats after equimolar single (6 moles/kg) or multiple (6x6 moles/kg) drug application. Drug concentrations were determined in plasma and various target organs of the drugs, e.g. heart, muscle, lung and brain, after drug application in the light period (L) and dark period (D), respectively. After single drug administration pharmacokinetic parameters of all drugs depended on the L and D conditions. Elimination half-lives in plasma and organs were shorter during D than during L. No L-D-differences were found in initial drug concentrations of the hydrophilic drugs sotalol and atenolol. In contrast, C0-values of the lipophilic propranolol in highly perfused organs (muscle, lung, brain) and of metoprolol in muscle tissue were significantly higher in D than in L. No obvious temporal dependency was found in other pharmacokinetic parameters (AUC, plasma clearance,V
d) with the exception inV
d of propranolol. Due to the different physico-chemical properties of the compounds inter-drug-differences in pharmacokinetic parameters including drug accumulation into lung and brain tissue were observed. Multiple drug dosing abolished the circadian-phase-dependency in the elimination half-lives of the drugs due to an increase in D. Only for the highly lipophilic propranolol half-lives in highly perfused organs were still shorter in D than in L. It is concluded that L-D-differences in drug half-lives after single dose application are mainly due to circadian variations in drug elimination with a higher hepatic (propranolol, metoprolol) or renal (sotalol, atenolol) elimination in the activity period of rats during D. Additional studies with propranolol on heart rate of conscious rats revealed that a maximum in -receptor blockade was achieved at 10 moles/kg in L but not in D. Thus, it is assumed that abolition of circadian-phase-dependency in half-lives after 6x6 moles/kg of the drugs may be due to the longer lasting and more pronounced -receptor blockade after multiple drug dosing over a period of several hours in D. Thereby, liver-flow-dependent elimination of propranolol and metoprolol and renal elimination of sotalol and atenolol is reduced to base-line levels found in L.Parts of this work were presented at the 22nd Spring Meeting (Lemmer 1981) and at the Joint Meeting (Lemmer et al. 1983a) of the German Pharmacological Society 相似文献
32.
33.
单片微机化微弱发光测量仪及其在肿瘤研究中的初步应用 总被引:2,自引:0,他引:2
单片微机化微弱发光测量仪由中科院生物物理所和北京科龙生物医学技术开发公司研制成功。该仪器适用于肿瘤研究中生物医学样品的微弱发光的测量。测量样品的重复性优于0.8%,稳定性优于0.5%,线性相关系数达0.9997,不仅可以进行样品的发光强度测量,还可以进行动力学曲线的测量以及样品发射光谱的测量。光谱在400nm-750nm范围内。测量方式可选择手动、半自动和自动计时三种。测量结果表明,荷瘤裸鼠血液微 相似文献
34.
目的:研究本地区临床分离结核杆菌rpoB基因突变与利福平(RFP)耐药性的关系。方法:对36株RFP敏感株和44株RFP耐药株rpoB基因的328bp的PCR扩增产物进行单链构象多态性(Single-strand comformationpolymorphism,SSCP)分析。结果:36株RFP敏感株的SSCP带谱均与参考株H37Rv相同,44株RFP耐药株中,25株高度RFP耐药株和11株低度RFP耐药株的SSCP带谱与H37Rv带谱有差异;另8株低度RFP耐药株的SSCP带谱与H37Rv带谱相同。结论:SSCP分析可检测出rpoB基因突变,该基因突变与本地区临床分离结核杆菌对RFP耐药有关。 相似文献
35.
4-Phenyl-1-(4-phenylbutyl)piperidine(4-PPBP) is a very potent ligand for σ (Sigma) receptors. The present study was undertaken to evaluate [3H]4-PPBPas a radioligand for in vivo labeling of cerebral σ receptors. After intravenous administration of [3H]4-PPBP to mice, there is high uptake of radioactivity in the brain. The regional distribution of radioactivity in the brain 2 h after intravenous injection of [3H]4-PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum ≥ prefrontal cortex ≥ parietal cortex > hypothalamus > olfactory tubercle ≥ thalamus > hippocampus > striatum). Pretreatment with haloperidol (2 mg/kg) significantly decreases the radioactivity measured in the brain 30–120 min after injection of [3H]4-PPBP. Pretreatment with unlabeled 4-PPBP or ifenprodil also significantly decreases radioactivity in the brain 2 h after injection of [3H]4-PPBP, in a dosedependent manner. The in vivo binding of [3H]4-PPBP in the brain also is significantly inhibited by SL 82.0715, BMY 14802, 1,3-di-o-tolylguanidine (DTG), and (+)-enantiomers of pentazocine, SKF 10,047, and 3-PPP, but not by the corresponding (?)-enantiomers, consistent with stereoselectivity of inhibition obtained in in vitro binding studies. In contrast, pretreatment with dizocilpine and spiperone does not inhibit in vivo binding of [3H]4-PPBP. The results indicate that [3H]4-PPBP would be a suitable radioligand for in vivo labeling of σ receptors in brain. © 1995 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America . 相似文献
36.
Jose Sänchez-Chapula 《Naunyn-Schmiedeberg's archives of pharmacology》1992,345(3):342-348
Summary The effects of the beta-adrenoceptor antagonist metoprolol on action potentials and membrane currents were studied in single guinea-pig ventricular myocytes. The experiments were carried out using the nystatin-method of whole-cell technique. This method was used in order to prevent the run-down of the calcium current. Metoprolol at concentrations of 10–100 mol/l shortened action potential in a dose-dependent way. The drug only decreased resting membrane potential at a concentration of 100 mol/1 in two out of five cells. Under voltage-clamp conditions, metoprolol blocked the high threshold calcium current at concentrations of 30 and 100 mol/l to 82 ± 4% and 73 ± 5% from control, respectively. The drug decreased the inward rectifying potassium current in a concentration-dependent manner. This effect was evident for inward current at voltages negative to the apparent reversal potential and for outward current at voltages between –30 and –80 mV. This blocking effect on the inward rectifying potassium current can explain the effect on resting membrane potential. At voltages positive to –30 mV metoprolol increased a time-independent outward current. This metoprolol-enhanced outward current was blocked by barium and cesium. This result suggests that the metoprolol-enhanced current is carried by potassium. The current component enhanced by metoprolol was not sensitive to glibenclamide and tetraethylammonium applied externally, which suggests that the adenosine triphosphate-sensitive channel is not the target of metoprolol. The activation of this time-independent outward current by metoprolol and the blocking effects on the calcium current seem to explain the shortening in action potential induced by the drug.
Send offprint requests to J. Sánchez-Chapula at the above address 相似文献
37.
Jeri W. Nieves Felicia Cosman Chris Mars Robert Lindsay 《Calcified tissue international》1992,51(5):352-355
Summary Forearm bone mineral density (BMD) was measured at proximal and distal sites by 125I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18–75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r=0.599–0.926; P0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements. 相似文献
38.
Summary Postganglionic neurones to the tail's skin of the cat were investigated with regard to their spontaneous activity, response characteristics to somatic stimuli and asphyxia, the conduction velocity of their axons, and the conduction velocity of the preganglionic axons converging on them. The cats were anaesthetized with chloralose, immobilized, and arteficially ventilated. With this regimen the postganglionic neurones were divided into two types: 1. Type 1 neurones are spontaneously active and exhibit reflexes upon somatic stimulation. During asphyxia they are mostly first depressed and then excited for about 2–3 min. Their axons conduct with 0.57±0.13 m/s (mean ± SD). The preganglionic axons converging on them conduct with 5.4±1.6 m/s. 2. Type 2 neurones are not spontaneously active and exhibit with few exceptions no reflexes on somatic stimuli. During asphyxia they are activated after 3–4 min, concomitantly with piloerection, when the activity in type 1 neurones is already decreasing. Their axons conduct with 0.84±0.14 m/s, the preganglionic axons converging on them conduct with 9.9±2.9 m/s. 3. From these characteristics it is concluded that type 1 neurones have vasomotor function and most type 2 neurones pilomotor function. 相似文献
39.
Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded. 相似文献
40.
Spontaneous improvement in reduced vasodilatory capacity in major cerebral arterial occlusive disease 总被引:4,自引:1,他引:3
Reduced vasodilatory capacity resulting from occlusive lesions of the major cerebral arteries may return to normal without
surgical revascularisation. We aimed to determine prospectively the frequency and predictors of recovery of impaired haemodynamics
as demonstrated by acetazolamide (ACZ) reactivity on single-photon emission computed tomography (SPECT). Vasoreactivity was
measured by 123I-IMP SPECT with an ACZ challenge, in 37 medically treated patients with unilateral occlusive disease of the internal carotid
or middle cerebral artery at an interval of 1–2 years. Each ACZ challenge test was analysed semiquantitatively by calculating
the degree of increase in cerebral blood flow (CBF) asymmetry after ACZ administration (ΔAI). Vasodilatory capacity was abnormal
initially in 20 patients (65 %); eight of whom (40 %) exhibited spontaneous normalisation on follow-up. Although the baseline
characteristics did not differ significantly between patients with or without increase in reactivity, logistic regression
analysis revealed that the initial ΔAI (P < 0.05) and the type of vascular lesion (stenosis or occlusion) (P < 0.05) correlated significantly with a return towards normal of reduced ACZ reactivity. Spontaneous improvement of impaired
vasodilatory capacity may not be a rare phenomenon. We found that mild reduction in the initial ACZ reactivity and a stenosis,
but not complete occlusion, were independent factors contributing to normalisation of impaired cerebral haemodynamics.
Received: 12 October 1998/Accepted: 27 April 1999 相似文献