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81.
目的 探究低氧状态下骨细胞对破骨细胞形成的作用及其机制。方法 用去铁胺甲磺酸(DFO)刺激骨细胞系MLO-Y4建立体外低氧骨细胞培养体系。CCK-8实验检测DFO对MLO-Y4细胞增殖活性的影响;采用DFO处理后的MLO-Y4细胞培养液制备条件培养基诱导RAW264.7细胞分化,行抗酒石酸酸性磷酸酶(TRAP)染色检测;利用实时荧光定量聚合酶链反应、细胞免疫荧光和蛋白质印迹(Western blot)检测DFO作用下MLO-Y4表达低氧诱导因子(HIF)-1α与核因子κB受体活化因子配体(RANKL)的情况;检测HIF-1α siRNA转染对MLO-Y4表达HIF-1α和RANKL的影响。结果 100 μmol·L -1 DFO作用24 h时MLO-Y4增殖活性升高,之后随着时间延长细胞增殖活性下降(P<0.01)。加入可溶性RANKL后,低氧组可见破骨细胞形成明显增加(P<0.001)。100 μmol·L -1 DFO作用下,HIF-1α mRNA表达稳定,RANKL mRNA的表达随时间明显变化,24 h时最高(P<0.01);HIF-1α、RANKL蛋白表达升高(P<0.01)。低氧状态下siHIF-1α转染可降低HIF-1α和RANKL的表达(P<0.01),破骨细胞减少(P<0.01)。结论 低氧状态下MLO-Y4可通过上调HIF-1α的蛋白水平促进RANKL的生成,进而加速RAW264.7细胞向破骨细胞分化。 相似文献
82.
Proof of the protective properties against cerebral hypoxic hypoxidosis of a new potentially nootropic drug, tenilsetam (TEN), were studied as compared with 5 mg co-dergocrine mesylate (CDM) in a double-blnd, placebo-controlled trial. Hypoxic hypoxidosis was induced by a fixed gas combination of 9.8% oxygen and 90.2% N2, equivalent to 6,000 m altitude, which was inhaled for 23 min under normobaric conditions by 15 healthy volunteers. They received randomized after an adapation session placebo, 150 mg, 300 mg, and 900 mg TEN and 5 mg CDM. Blood gases, quantitative EEG, and psychometric measures were obtained under normoxic (21% O2) and hypoxic (9.8% O2) conditions before as well as 2,4,6, and 8 hr after oral drug administration. Blood gas analysis demonstrated under hypoxia a drop in PO2 from 91 to 37 mm Hg and in PCO2 from 38 to 33 mm Hg, while pH increased from 7.41 to 7.47. Under these hypoxic conditions, computer-assisted spectral analysis of the EEG showed an increase of delta/theta, decrease of alpha, and increase of superimposed fast beta activity indicative of deterioration in vigilance. The latter was documented at the behavioral level by deterioration of intellectual and mnestic functions, psychomotor activity, performance in a reaction time task, mood, and wakefulness. Both TEN and CDM attenuated this brain dysfunction, although in a different manner. Whereas TEN induced an increase in alpha and decrease of fast beta activity as compared with placebo, 5 mg CDM attenuated delta/theta and increased alpha-adjacent beta activity. Multivariate analysis based on changes in all EEG-variables exhibited the highest dosage TEN and the reference substance significantly different from placebo. Psychometric data added—despite high variance—further evidence for antihypoxidotic/nootropic properties of both drugs, as psychometric performance under hypoxia deteriorated by 45% after placebo, while after 5 mg CDM, 150 mg, 300 mg, and 900 mg TEN only by 25, 27, 39, and 22%, respectively. Based on changes in all 12 psychometric variables obtained at all times, 900 mg, but also 150 mg TEN as well as 5 mg CDM, were significantly different from placebo. Under normoxic conditions, multivariate analyses did not show any significant differences to placebo, and only singular neurophysiological and behavioral changes were observed. 相似文献
83.
目的:分析胃肠道间质瘤临床常用的诊断与治疗方法,并对其方法的有效性、安全性进行研究。方法:选择2005年1月~2010年1月在本院进行了手术治疗的胃肠道间质瘤患者共65例作为治疗组,随机选择同一时段86例胃、结直肠癌患者做为对照组,比较分析治疗组与对照组的CT、消化道造影、内镜+活检资料的临床价值。将该组胃肠道间质瘤患者按照手术后是否服用甲磺酸伊马替尼分为两组,治疗组:手术+甲磺酸伊马替尼,对照组:手术。分析二者在疗效上的差异。结果:CT、消化道造影、内镜+活检等临床资料显示出能够帮助诊断的显著性的差异。是否服用甲磺酸伊马替尼在复发、转移、生存时间等方面具有显著性差异。结论:临床资料不能确诊胃肠道间质瘤,但能够提供相当准确的临床诊断;GIST术后复发率很高,甲磺酸伊马替尼对防止转移、复发、延长生存时间有良好的疗效。 相似文献
84.
The objective of the present investigation was to separate, identify and characterize the major degradation products (DPs) of nelfinavir mesylate generated under hydrolytic, oxidative, photolytic and thermal stress conditions as advised in International Conference on Harmonization (ICH) guideline Q1A(R2). The drug was found to degrade under acidic, basic, oxidative and photolytic stress, while it was stable in neutral and thermal stress conditions. A total of three degradation products were formed, which were separated on a C-18 column employing a gradient HPLC method. A complete mass fragmentation pathway of the drug was first established with the help of multi-stage (MS(n)) and MS/TOF accurate mass studies. Then stressed samples were subjected to LC-MS/TOF studies, which provided their fragmentation pattern and accurate masses. The mass spectral data were employed to characterize the DPs and assign structures to them. The total information was also used to establish the degradation pathway of the drug. The degradation products were identified as 3-hydroxy-N-((2R,3R)-3-hydroxy-1-(phenylthio)butan-2-yl)-2-methylbenzamide and (3S,4aS,8aS)-N-tert-butyl-2-((2R,3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzamido)-4-(phenylsulfinyl)butyl)decahydroisoquinoline-3-carboxamide. 相似文献
85.
目的:探讨甲磺酸罗哌卡因用于幼儿臂丛神经阻滞的最佳浓度。方法:将80例行臂丛神经阻滞的幼儿患者,随机分为4组,每组20例。均在全麻下用甲磺酸罗哌卡因。浓度分别为0.33%、0.25%、0.20%、0.167%,容量为1ml/kg,观察临床麻醉效果及不良反应。结果:0.167%组浓度较低,阻滞效果较其他三组差。0.33%组有2例出现肢体不自主运动。结论:0.2%、0.25%、0.33%甲磺酸罗哌卡因均可以安全地用于幼儿臂丛神经阻滞,0.33%甲磺酸罗哌卡因要注意防止局麻药中毒。 相似文献
86.
87.
BackgroundThe aim of the study was to determine the type of interaction between pregabalin (a 3rd-generation antiepileptic drug) and WIN 55,212-2 mesylate (WIN – a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) administered in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice.MethodsLinear regression analysis was used to evaluate the dose-response relationships between logarithms of drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, doses were calculated that increased the antinociceptive effect by 30% (ED30 values) for pregabalin, WIN, and their combination. The type of interaction between pregabalin and WIN was assessed using the isobolographic analysis.ResultsResults indicated that both compounds produced a definite antinociceptive effect, and the experimentally-derived ED30 values for pregabalin and WIN, when applied alone, were 29.4 mg/kg and 10.5 mg/kg, respectively. With isobolography, the experimentally derived ED30 mix value for the fixed ratio combination of 1:1 was 5.7 mg/kg, and differed significantly from the theoretically calculated ED30 add value of 19.95 mg/kg (p < 0.01), indicating synergistic interaction between pregabalin and WIN in the hot-plate test in mice.ConclusionsIsobolographic analysis demonstrated that the combination of WIN with pregabalin at a fixed ratio of 1:1 exerted synergistic interaction in the mouse model of acute thermal pain. If the results from this study could be adapted to clinical settings, the combination of WIN with pregabalin might be beneficial for pain relief in humans. 相似文献
88.
Wcislo G Szarlej-Wcislo K Szczylik C 《Journal of cancer research and clinical oncology》2007,133(8):533-538
Objective There has been only one report available that focuses on the treatment with imatinib mesylate of two individual persons with
aggressive fibromatosis. The authors concluded that after long-term treatment, for 9 and 11 months, with imatinib mesylate,
both patients demonstrated radiographic and clinical responses. The novel therapy should be considered as salvage in patients
with aggressive fibromatosis expressed platelet-derived growth factor receptor—alfa, beta (PDGFR-alfa, PDGFR-beta), and/or
c-kit, whose tumors are uncontrollable by the standard management. On the other hand, the number of kinases blocked by imatinib
mesylate is notching up, for instance the tyrosine kinase, which is associated with macrophage-colony stimulating factor receptor
(M-CSFR).
Methods The patient was suffering from aggressive fibromatosis after prior therapy including surgery (R2), radiotherapy, and systemic
treatment with combination of tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c-kit (CD117),
and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and beta were not assessed. The tests for both assessed molecules
revealed negative results. In spite of this, the patient underwent a unique treatment with imatinib mesylate at the dose of
400 mg orally once daily for 3 years and 2 months.
Results After three months of the therapy, radiographic (met criteria of SD but small decrease of the tumor was noted) and clinical
responses were recorded for the first time. The same was seen after 6 and 13 months of therapy continuation with imatinib
mesylate. Currently, the patient is treated with imatinib mesylate (400 mg orally once daily) without any toxicity effects.
The last MRI revealed readily a smaller tumor (35 × 20 mm) after such a therapy lasted more than 3 years.
Conclusions Treatment with imatinib mesyalte has been a well-accepted therapy for chronic myelagenous leukemia (CML) and gastrointestinal
stromal tumors (GIST). There have been established four kinases (p210bcr/abl, c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other potential targets will be discovered
as it has lately been determined that M-CSFR kinase activity was blocked by imatinib mesylate. The salvage therapy for aggressive
fibromatosis with imatinib mesylate seems to be an attractive opportunity for patients with the advanced disease, whose prior
therapy failed. 相似文献
89.
Ueki T Otani K Kawamoto K Shimizu A Fujimura N Sakaguchi S Matsui T 《Journal of gastroenterology》2007,42(2):161-167
Background It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention
of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin
and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare
the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis.
Methods Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization
into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150 000 units) or gabexate mesylate (600 mg),
beginning 60–90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP
pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain.
Results The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and
one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis.
There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups.
Conclusions There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate
on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence
of post-ERCP pancreatitis. 相似文献
90.
Recently, a series of studies have given rise to and provided evidence for the hypothesis that the nucleus submedius (Sm) in the medial thalamus is involved in modulation of nociception. The Sm, ventrolateral orbital cortex (VLO) and the periaqueductal gray (PAG) constitute a pain modulatory pathway, activation of which leads to activation of the PAG–brainstem descending inhibitory system and depression of the nociceptive inputs in the spinal cord and trigeminal nucleus. Other studies have indicated that the Sm–VLO–PAG pathway plays an important role in the analgesia induced by electroacupuncture stimulation of the acupuncture point (acupoint) for exciting small diameter fiber (A-δ and C group) afferents. Opioid peptides, serotonin, dopamine, glutamate and their related receptors are involved in Sm- and/or VLO-mediated descending antinociception, and a GABAergic disinhibitory mechanism participates in mediating the antinociception induced by activation of μ-opioid receptors, serotonin 1A receptors, and dopamine D2-like receptors. This review describes these findings, which provide important new insights into the roles of the thalamus and cerebral cortex in descending pain modulation. 相似文献