全文获取类型
收费全文 | 473篇 |
免费 | 14篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 43篇 |
妇产科学 | 2篇 |
基础医学 | 89篇 |
口腔科学 | 6篇 |
临床医学 | 43篇 |
内科学 | 88篇 |
皮肤病学 | 10篇 |
神经病学 | 41篇 |
特种医学 | 38篇 |
外科学 | 45篇 |
综合类 | 8篇 |
预防医学 | 22篇 |
眼科学 | 8篇 |
药学 | 18篇 |
肿瘤学 | 17篇 |
出版年
2020年 | 4篇 |
2018年 | 5篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 7篇 |
2010年 | 18篇 |
2009年 | 12篇 |
2008年 | 18篇 |
2007年 | 22篇 |
2006年 | 9篇 |
2005年 | 8篇 |
2004年 | 21篇 |
2003年 | 19篇 |
2002年 | 13篇 |
2001年 | 8篇 |
2000年 | 11篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 16篇 |
1989年 | 15篇 |
1988年 | 23篇 |
1987年 | 16篇 |
1986年 | 13篇 |
1985年 | 17篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1976年 | 10篇 |
1975年 | 5篇 |
1973年 | 5篇 |
1971年 | 3篇 |
1969年 | 5篇 |
1968年 | 6篇 |
1966年 | 5篇 |
排序方式: 共有487条查询结果,搜索用时 15 毫秒
81.
S Sinha S Gupta S Malhotra NS Krishna AV Meru V Babu V Bansal M Garg N Kumar A Chugh A Ray 《British journal of pharmacology》2010,160(5):1119-1127
Background and purpose:
AE9C90CB (N- [(1R, 5S, 6R)-3-azabicyclo [3.1.0] hex-6-ylmethyl]-2-hydroxy-N-methyl-2, 2-diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe the in vitro and in vivo profiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin).Experimental approach:
Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity.Key results:
In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M3 muscarinic receptors with pKi of 9.90 ± 0.11 and was 20-fold more selective for M3 than for M2 muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pKB, 9.13 ± 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin.Conclusions and implications:
We have identified AE9C90CB, a compound exhibiting moderate selectivity for M3 over M2 receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs. 相似文献82.
83.
目的:中性粒细胞粘附在缺血再灌注损伤中有非常重要的作用。本文用SD大鼠趾长屈肌缺血再灌注损伤模型,观察L一粘附素单抗LAM1—116在缺血再灌注损伤中的作用。方法:30只SD大鼠被均分为2组:LAM1—116组和生理盐水对照组。每只大鼠的一侧趾长屈肌作为正常对照,另外一侧进行 3 h缺血 4 h再灌注。结果:LAM1— 116组实验侧的髓过氧化物酶为正常的2倍(2.3±2.2),生理盐水对照组则为正常的28倍(27.5±11.7)(P<0.001);LAM1—116组的湿重比(1.10± 0.10)、疲劳肌力(77. 1%±12.1%)与对照组相比(分别为 1. 23± 0. 10和 49. 7%± 9 .3%)明显改善(P< 0.05);组织学上,LAM1—116组的中性粒细胞局部浸润显著减少,水肿减轻。结论:通过 L-粘附素单克隆抗体 LAM1— 116阻断 L-粘附素的功能,可以有效地降低中性粒细胞在再灌注肌肉中的浸润,防止组织水肿,从而改善肌肉的功能。 相似文献
84.
Warkentin TE; Hayward CP; Boshkov LK; Santos AV; Sheppard JA; Bode AP; Kelton JG 《Blood》1994,84(11):3691-3699
Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia. 相似文献
85.
Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA 总被引:2,自引:0,他引:2
Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state. 相似文献
86.
Headache in lacunar stroke 总被引:1,自引:0,他引:1
The presence of headache within a 72-h interval of stroke onset was investigated in a cohort of 145 lacunar infarcts. Fourteen (10%) experienced diffuse or bilateral headache. Hypertension was less frequent (43 vs 76%; 95% CI: 6 to 60%) and of shorter duration (2.4 vs 7.8 years; t = 2.29; p = 0.02) among patients with headache. Leukoaraiosis was less frequent (40% vs 71%; 95% CI: −57 to −7%) and severe (7 vs 24%; 95% CI: −33 to −2%) in patients with headache. Age, sex, stroke risk factors, type of lacunar stroke, mode of onset, stroke severity, ultrasound and other CT findings were similar in patients with and without headache. No differences in the sixth month neurological or functional outcome were detected between lacunar patients with and without headache. Headache in lacunar stroke cannot be predicted by the clinical characteristics of the stroke and is not due to coexisting cardiembolism, intra or extracranial disease. Hypertensive small-vessel disease is less common and severe in lacunar strokes with associated headache. 相似文献
87.
The relationship between urinary calcium, sodium, and potassium excretion and the role of potassium in treating idiopathic hypercalciuria 总被引:1,自引:0,他引:1
OBJECTIVES: 1) To evaluate the relationships between urinary sodium (UNa), potassium (UK), and calcium (UCa) excretion in the pediatric population; and 2) to determine the effect of increasing potassium intake in patients with idiopathic hypercalciuria and investigate whether this intervention can be offered as another mode of therapy in this patient population. DESIGN: Prospectively, we determined UNa, UK, UCa, and creatinine (Cr) concentrations in randomly collected urine samples from children on initial evaluation for urinary frequency, dysuria, hematuria, enuresis, or kidney stones to identify children with hypercalciuria. SETTING: The outpatient renal clinic of an academic hospital. PARTICIPANTS: Twenty-three black children (13 girls and 10 boys) and 77 white children (44 girls and 33 boys) 3.92 to 16.67 years of age. INTERVENTIONS: Eleven children with hypercalciuria were given potassium supplementation or placed on a high-potassium diet for at least 2 weeks. OUTCOME MEASURES: UNa to UK, UNa to Cr, UK to Cr, and UCa to Cr ratios were calculated from measured levels of urinary minerals. These were repeated in 11 hypercalciuric patients after 2 weeks of increased potassium intake. RESULTS: A total of 100 urine samples were analyzed. The UCa/Cr ratio in blacks 0.04 +/- 0.06 (mean +/- standard deviation) was significantly lower than in whites 0.16 +/- 0.12. There were 21 hypercalciuric white children versus only 1 black child. Linear regression analysis revealed a positive direct correlation between UNa/Cr and UCa/Cr in all 100 subjects and in whites alone but not in blacks. An inverse relationship existed between UK/Cr and UCa/Cr in all subjects and in whites and showed a strong trend in blacks. A marked direct relationship was found between UNa/K and UCa/Cr in all subjects (r = .43) as well as in whites (r = .59) and blacks (r = .49). One black child and 10 white hypercalciuric children were treated with "extra" K for at least 2 weeks. The UNa/K decreased from 4.73 +/- 2.28 to 1.98 +/- 1.09, and the UCa/Cr decreased from 0. 31 +/- 0.10 to 0.14 +/- 0.07, with resolution or improvement of the patients' symptoms. CONCLUSIONS: In our patient population with urinary symptoms, the UCa/Cr ratio in black children is lower and hypercalciuria less common than in white children. In both white and black populations, the UNa/K ratio had the strongest association with the UCa/Cr ratio, indicating an opposing role of UNa and UK on the UCa/Cr ratio. Increased potassium intake was found to be beneficial for hypercalciuric children by decreasing the UNa/K ratio and, consequently, the UCa/Cr ratio. 相似文献
88.
V. A. Berezin V. M. Zaides A. F. Artamonov E. S. Isaeva V. M. Zhdanov 《Archives of virology》1985,85(3-4):281-300
Summary The isolation of ortho- and paramyxovirus glycoproteins using a new nonionic detergent (MESK) is reported. MESK was shown to solubilize most of the viral envelope glycoproteins without decreasing their biologic activity. Solubilized glycoproteins are not contaminated by any internal viral proteins or by appreciable quantities of viral envelope lipids. The removal of MESK by dialysis resulted in the formation of glycoprotein micelles. The immunogenic activity of isolated glycoproteins was compared to that of virus particles. Immunization with isolated glycoproteins was shown to protect mice against a lethal influenea infection. Virions were treated with MESK in the presence of exogenous egg phosphatidylcholine, detergent was removed by dialysis and the glycoprotein was reconstituted in the vesicles. This reconstitution was accompanied by restoration of the haemolytic activity of Sendai virus proteins up to that of native virus particles. The level of activity, also the morphology and buoyant density of the vesicle were dependent on the protein/lipid ratio. MESK proved to be of value for the selective solubilization of the surface glycoproteins of animal enveloped viruses and their reconstitution in liposomes.With 6 Figures 相似文献
89.
Thomas E. Maar Lars C.B. Rnn Elisabeth Bock Vladimir Berezin Julio Moran Herminia Pasantes-Morales Arne Schousboe 《Journal of neuroscience research》1997,47(2):163-172
Microwell cultures of dissociated tissue from prenatal rat hippocampus and cerebral cortex as well as from early postnatal cerebellum were used for quantification of neuronal aggregation, process extension, and fasciculation. It was shown that the cells in culture from these different brain regions developed differently with regard to both architecture and rate of differentiation. The effect of a polyclonal antibody against the neural cell adhesion molecule (NCAM), the excitatory amino acid receptor agonist N-methyl-D-aspartate (NMDA), and the neurotoxin acrylamide on aggregation and fiber formation was investigated. Exposure to the NCAM antibody led to formation of fewer but larger aggregates and stimulated the morphological development of the cultures. Acrylamide affected aggregate formation, leading to smaller but more numerous aggregates, and it inhibited process extension and fasciculation. Treatment with NMDA affected process formation and led to formation of more numerous but smaller aggregates. Some of these effects were strongly tissue-dependent. Thus, large differences were seen regarding the effect of the NCAM antibody on aggregation and process extension in cultures from the different brain areas. The culture systems appear to represent convenient and reliable screening tools to study the influence of putative morphoregulatory substances on cell-cell interactions during early neuronal development. J. Neurosci. Res. 47:163–172, 1997. © 1997 Wiley-Liss, Inc. 相似文献
90.
Mathieu L. Viger Wangzhong Sheng Cathryn L. McFearin Mikhail Y. Berezin Adah Almutairi 《Journal of controlled release》2013
Though accurately evaluating the kinetics of release is critical for validating newly designed therapeutic carriers for in vivo applications, few methods yet exist for release measurement in real time and without the need for any sample preparation. Many of the current approaches (e.g. chromatographic methods, absorption spectroscopy, or NMR spectroscopy) rely on isolation of the released material from the loaded vehicles, which require additional sample purification and can lead to loss of accuracy when probing fast kinetics of release. In this study we describe the use of time-resolved fluorescence for in situ monitoring of small molecule release kinetics from biodegradable polymeric drug delivery systems. This method relies on the observation that fluorescent reporters being released from polymeric drug delivery systems possess distinct excited-state lifetime components, reflecting their different environments in the particle suspensions, i.e., confined in the polymer matrices or free in the aqueous environment. These distinct lifetimes enable real-time quantitative mapping of the relative concentrations of dye in each population to obtain precise and accurate temporal information on the release profile of particular carrier/payload combinations. We found that fluorescence lifetime better distinguishes subtle differences in release profiles (e.g. differences associated with dye loading) than conventional steady-state fluorescence measurements, which represent the averaged dye behavior over the entire scan. Given the method's applicability to both hydrophobic and hydrophilic cargo, it could be employed to model the release of any drug-carrier combination. 相似文献