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101.
Jan Buschbaum Linda Freitag Theodor F. Slongo Stephan Zeiter Michael Schütz Markus Windolf 《Journal of children's orthopaedics》2021,15(2):137
PurposeVarus-valgus deformities in children and adolescents are often corrected by temporary hemi-epiphysiodesis, in which the physis is bridged by an implant to inhibit growth. With standard implant solutions, the acting forces cannot be regulated, rendering the correction difficult to control. Furthermore, the implant load steadily increases with ongoing growth potentially leading to implant-related failures. A novel implant concept was developed applying a controlled constant force to the physis, which carries the potential to avoid these complications. The study aim was to proof the concept in vivo by analyzing the effect of three distinct force levels on the creation of varus deformities.MethodsThe proposed implant is made of a conventional cerclage wire and features a twisted coil that unwinds with growth resulting in an implant-specific constant force level. The proximal medial tibial physes of 18 lambs were treated with the implant and assigned to three groups distinct by the force level of the implant (200 N, 120 N, 60 N).ResultsThe treatment appeared safe without implant-related failures. Deformity creation was statistically different between the groups and yielded on average 10.6° (200 N), 4.8° (120 N) and 0.4° (60 N) over the treatment period. Modulation rates were 0.51°/mm (200 N), 0.23°/mm (120 N) and 0.05°/mm (60 N) and were constant throughout the treatment.ConclusionBy means of the constant force concept, controlled growth modulation appeared feasible in this preclinical experiment. However, clinical trials are necessary to confirm whether the results are translatable to the human pathological situation. 相似文献
102.
103.
Ilkka Pörsti Markus Hecker Eberhard Bassenge Rudi Busses 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(6):650-658
Summary We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor NG-nitro-L-arginine (30 mol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.In conclusion, AII induced a biphasic pressor response in the rabbit coronary vascular bed consisting of a transient vasoconstriction followed by a dilatation especially at higher concentrations of AII, an effect which was independent of the endothelial autacoids nitric oxide and PGI2. The AII-induced dilatation probably reflected rapid desensitization of the coronary arterial smooth muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT, receptor subtype localized on coronary endothelial and smooth muscle cells, as well as on cardiomyocytes.On leave from the Department of Biomedical Sciences, University of Tampere, P.O. Box 607, FIN-33101 Tampere, FinlandCorrespondence to: I. Pörsti 相似文献
104.
Alexander Mülsch Markus Hecker Petr I. Mordvintcev Anatoly F. Vanin Rudi Busse 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(1):92-100
Summary The molecular mechanism(s) underlying the vasodilator activity of CAS 936 (3-(cis-2,6-dimethylpiperidino)-N-(4-methoxybenzoyl)-sydnonimine) and its metabolites 3-(cis-2,6-dimethylpiperidino)-sydnonimine (C87 3754) and N-(cis-2,6-dimethylpiperidino)-N-nitroso-2-aminoacetonitril (C873786) was investigated. These compounds were tested for their relaxant activity in isolated rabbit arterial segments, activation of purified soluble guanylyl cyclase and release of nitric oxide (NO) in vitro and in vivo. C873754 and C873786 inhibited the noradrenalin-induced contraction and increased the cyclic GMP content of endothelium-denuded rabbit aortic and femoral segments, whereas CAS 936 was without effect. Similarly, both metabolites, but not CAS 936, activated purified soluble guanylyl cyclase (EC50 about 30 M) and released NO in buffered aqueous solutions, as detected by electron spin resonance (esr) spectrometry. Both in vitro and in vivo an accumulation of NO was detected by esr spectrometry in vascular tissues exposed to the metabolites of CAS 936, whereas a significant release of NO from CAS 936 was only detected in the isolated rabbit liver, but not in vascular tissue. It is conceivable, therefore, that the metabolites of CAS 936 appearing in the systemic circulation after hepatic biotransformation induce vasodilatation by release of NO and activation of soluble guanylyl cyclase in vascular smooth muscle. Moreover, the activation of soluble guanylyl cyclase in vitro by the metabolites of CAS 936 was significantly enhanced by co-incubation with certain particulate fractions from bovine aortic endothelial and smooth muscle cells. Thus, an enzymic release of NO from these metabolites in addition to their spontaneous decomposition may play a significant role for their vasodilator activity in vivo.Correspondence to A. Mülsch at the above address 相似文献
105.
Fabian F Moebius Raphael J Reiter Markus Hanner Hartmut Glossmann 《British journal of pharmacology》1997,121(1):1-6
- The sigma-drug binding site of guinea-pig liver is carried by a protein which shares significant amino acid sequence similarities with the yeast sterol C8–C7 isomerase (ERG2 protein). Pharmacologically - but not structurally - the sigma1-site is also related to the emopamil binding protein, the mammalian sterol C8–C7 isomerase. We therefore investigated if sterol C8–C7 isomerase inhibitors are high affinity ligands for the (+)-[3H]-pentazocine labelled sigma1-binding site.
- Among the compounds which bound with high affinity to native hepatic and cerebral as well as to yeast expressed sigma1-binding sites were the agricultural fungicide fenpropimorph (Ki 0.005 nM), the antihypocholesterinaemic drugs triparanol (Ki 7.0 nM), AY-9944 (Ki 0.46 nM) and MDL28,815 (Ki 0.16 nM), the enantiomers of the ovulation inducer clomiphene (Ki 5.5 and 12 nM, respectively) and the antioestrogene tamoxifen (Ki 26 nM).
- Except for tamoxifen these affinities are essentially identical with those for the [3H]-ifenprodil labelled sterol C8–C7 isomerase of S. cerevisiae. This demonstrates that sigma1-binding protein and yeast isomerase are not only structurally but also pharmacologically related. Because of its affiliations with yeast and mammalian sterol isomerases we propose that the sigma1-binding site is localized on a sterol isomerase related protein, involved in postsqualene sterol biosynthesis.
106.
Madörin Maya van Hoogevest Peter Hilfiker Rolf Langwost Birgit Kresbach Gerhard M. Ehrat Markus Leuenberger Hans 《Pharmaceutical research》1997,14(12):1706-1712
Purpose. The applicability of Asymmetrical Flow Field-Flow Fractionation (Asymmetrical Flow FFF) as an alternative tool to examine the distribution of a lipophilic drug (N-Benzoyl-staurosporine) within human plasma protein fractions was investigated with respect to high separation speed and loss of material on surfaces due to adsorption.
Methods. Field-Flow Fractionation is defined as a group of pseudo-chromatographic separation methods, where compounds are separated under the influence of an externally applied force based on differences in their physicochemical properties. This method was used to separate human plasma in its protein fractions. The drug distribution in the fractions was investigated by monitoring the fractionated eluate for drug content by fluorescence spectroscopy.
Results. Human plasma was separated into human serum albumin (HSA), high density lipoprotein (HDL), 2-macroglobulin and low density lipoprotein (LDL) fractions in less than ten minutes. Calibration of the system and identification of the individual fractions was performed using commercially available protein reference standards. The influence of membrane type and carrier solution composition on the absolute recovery of N-Benzoyl-staurosporine and fluorescein-isothio-cyanate-albumin (FITC-albumin) was found to be quite significant. Both factors were optimized during the course of the investigations. N-Benzoyl-staurosporine was found to be enriched in the fraction containing HSA.
Conclusions. If experimental conditions are thoroughly selected and controlled to suppress drug and plasma protein adsorption at the separation membrane, Asymmetrical Flow FFF shows high recoveries and fast separation of human plasma proteins, and can be a reliable tool to characterize drug / plasma protein interactions. For analytical purposes it has the potential to rival established technologies like ultracentrifugation in terms of ease-of-use, precision, and separation time. 相似文献
107.
Heiko Kilter Olaf Lenz Karl La Rosée Markus Flesch Robert H. G. Schwinger Martin Mädge Ferdinand Kuhn-Regnier Michael Böhm 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(3):308-312
Nitric oxide (NO) has been reported to mediate several effects in response to muscarinic cholinergic stimulation in cardiovascular tissues. Recently, an attenuation of guinea pig cardiac myocyte contraction by NO has been described. The aim of the present study was to determine whether the indirect negative inotropic effect of M-cholinoceptor stimulation in human myocardium is in part due to an effect of endogenous NO. Therefore, the effect of carbachol was studied under control conditions and during inhibition of NO-synthase by pretreatment with NG-monomethyl-l-arginine (NMMA). Functional experiments were performed in isolated, electrically driven (1 Hz, 37°C) left ventricular papillary muscle strips of human myocardium. Since cytokines have been reported to be increased in the serum of patients with heart failure and could induce NO-synthase activity in failing myocardium, we compared samples from nonfailing and terminally failing (classified as NYHA IV) hearts. The indirect negative inotropic effect of carbachol (10 mol/l) was studied in the presence of the \-adrenoceptor agonist isoprenaline (0.03 mol/l).After stimulation with isoprenaline, carbachol significantly (P < 0.05) reduced force of contraction. This effect was diminished in failing myocardium compared to nonfailing, probably due to the diminished inotropic response most likely due to the lower cAMP levels in response to \-adrenoceptor stimulation in the former condition. Pretreatment with NMMA (100 mol/l) altered the antiadrenergic effect of carbachol neither in nonfailing nor in failing preparations. Furthermore, inhibition of guanylyl cyclase, the target enzyme of NO, by preincubation with methylene blue (10 mol/l) for 30 min had no effect on the carbachol-induced decrease in force of contraction. Basal force of contraction, as well as the positive inotropic effect of isoprenaline remained unaffected by NMMA or methylene blue.The present study provides evidence that the indirect negative inotropic effect of M-cholinoceptor agonists is not due to an effect of NO in the human myocardium. Furthermore, the well known enhancement of cGMP in response to M-cholinoceptor stimulation appears not to be involved in this antiadrenergic effect. 相似文献
108.
Cognitive performance has been found to decline after exposure to stress, particularly in stress-prone subjects. The present study investigated whether a carbohydrate-rich, protein-poor (CR/PP) diet, which may enhance cerebral serotonin function in stress-prone subjects due to increases in the available tryptophan, improves the performance of stress-prone subjects after exposure to acute laboratory stress. Twenty-two high-stress-prone (HS) subjects and twenty-one low-stress-prone (LS) subjects aged between 19 and 26 years performed a memory scanning task after controllable and uncontrollable stress, following either a CR/PP diet or a protein-rich, carbohydrate-poor (PR/CP) isoenergetic diet. Uncontrollable stress reduced feelings of control (F(1,38) 9.30; P = 0.004), whereas pulse rate and skin conductance increased after both stress tasks (F(1,38) 78.34; P = 0.0005 and F(1,37) 83.16; P = 0.0004). Diet, stress-proneness and stress-controllability interacted (F(1,36) 9.46; P = 0.004) in such a way that performance in HS subjects was better with the CR/PP diet than with the PR/CP diet, but only after controllable stress. As the CR/PP diet has been found to increase the plasma tryptophan:large neutral amino acids ratio, indicating an increased availability of cerebral tryptophan and, thus, higher serotonin levels, it appears that there may be an increased availability of brain serotonin in HS subjects after controllable laboratory stress. 相似文献
109.
110.
Grünewald V Höfner K Thon WF Kuczyk MA Jonas U 《Restorative neurology and neuroscience》1999,14(2-3):189-193
Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives. 相似文献