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31.
The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing. 相似文献
32.
经临床鉴定静脉内注射小儿氨基酸对治疗胎儿宫内发育迟缓具有肯定效果。在B超监视下,使用小儿氨基酸的孕妇组于用药期间,胎儿生长参数BPD和HC显著高于使用成人氨基酸的孕妇组。10例足月娩出胎儿体重均达到甚至超过2.5kg。由此得出结论:使用小儿氨基酸注射液对于改善胎儿宫内发育迟缓优于成人氨基酸。 相似文献
33.
为了探讨精神分裂症患者治疗期间多巴胺的变化,我们选择舒必利治疗组20例,非舒必利治疗组10例作为病例组;15例非精神病患者作为对照组;检测脑脊液中多巴胺代谢产物高香草酸的含量;结果显示两组无显著性差异。精神分裂症患者治疗后舒必利组高香草酸含量升高,非舒必利组则降低,进一步分析显示舒必利治疗组非显效者较显效者治疗后高香草酸显著升高。提示机体对药物阻滞多巴胺受体后代偿反应的强弱与疗效有一定关系。 相似文献
34.
为证明癫痫发作早期一氧化氮(NO)抗发作效应,用NO合酶(NOS)抑制剂L-硝基精氨酸甲酯(L-NAME)对大鼠红藻氨酸(KA)诱导性发作进行干预,同时用分光光度法检测海马结构中NOS活性的早期变化。发现KA发作10min、30min组海马结构中NOS活性明显升高,而KA注射前30min给予L-NAME可显著抑制NOS活性的升高,这种抑制效应与大鼠KA发作中湿狗样摇动(WDS)的提早出现和发生次数增多显著相关。结果提示在KA诱导大鼠发作早期内源性NO具有明显的抗发作效用。 相似文献
35.
The database of the Hungarian randomised controlled trial of periconceptional multivitamin supplementation for the prevention of neural-tube defects was used to evaluate the length of the pre- and postovulatory phases of the menstrual cycle before and during multivitamin supplementation. The female cycle was more regular (i.e., the variance was lower) during the multivitamin supplementation. 相似文献
36.
Effect of isoelectric point on biodistribution and inflammation imaging with indium-111-labelled IgG
Caroline I. ten Kate Alan J. Fischman Robert H. Rubin A. J. Fucello D. Riexinger Robert A. Wilkinson Lina Du Ban An Khaw H. William Strauss 《European journal of nuclear medicine and molecular imaging》1990,17(6-8):305-309
Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge on the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its iso electric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats withEscherichia coli thigh infections. The biodistribution was significantly affected by pl. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3–2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs. 相似文献
37.
E. Angelini M. Teixeira J.-M. Aran E. Ferrary 《European archives of oto-rhino-laryngology》1998,255(7):331-333
Taurine is a β-aminosulfonic acid and is a ubiquitous amino acid whose role in the cochlea is not well established. In this
study, its entry from blood into perilymph was investigated in the guinea pig as animal model. The penetration rate of [3H]taurine (molecular weight 125) into the perilymph of the scala vestibuli was measured 1 and 2 h after the intravenous infusion
of [3H]taurine in nephrectomized animals. Results showed a rate of penetration in perilymph related to plasma at 36 ± 4.7% (n = 5) after 1 h and 43 ± 5.6% (n = 5) after 2 h. Compared to the penetration rate of urea (molecular weight 60) and mannitol (molecular weight 186) reported
previously in rats, a passive entry of taurine into perilymph through the blood-perilymph barrier is suggested.
Received: 30 July 1997 / Accepted: 15 January 1998 相似文献
38.
39.
Gérald Vanzetto Marc Janier Daniel Fagret Luc Cinotti Xavier André-Fouet Michel Comet Jacques Machecourt 《European journal of nuclear medicine and molecular imaging》1997,24(2):170-178
The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18
fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less
accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed
as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA)
as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and
to evaluate its contribution compared with the201Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection201T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction.
Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75
of maximum uptake on stress201T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves
for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)201T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly
considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that201T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85
and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and201T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold
(NS). When only the 177 severely hypoperfused segments were considered,201T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold),
while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs201T1 reinjection). In all circumstances, MIHA was less specific than201T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA
accurately detects the persistence of metabolic viability, but is not superior to201T1. 相似文献
40.