全文获取类型
收费全文 | 527篇 |
免费 | 33篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 26篇 |
妇产科学 | 18篇 |
基础医学 | 68篇 |
口腔科学 | 4篇 |
临床医学 | 34篇 |
内科学 | 104篇 |
皮肤病学 | 3篇 |
神经病学 | 139篇 |
特种医学 | 10篇 |
外科学 | 22篇 |
综合类 | 2篇 |
预防医学 | 41篇 |
眼科学 | 5篇 |
药学 | 42篇 |
肿瘤学 | 42篇 |
出版年
2023年 | 8篇 |
2022年 | 9篇 |
2021年 | 25篇 |
2020年 | 21篇 |
2019年 | 14篇 |
2018年 | 25篇 |
2017年 | 12篇 |
2016年 | 17篇 |
2015年 | 13篇 |
2014年 | 15篇 |
2013年 | 36篇 |
2012年 | 38篇 |
2011年 | 41篇 |
2010年 | 24篇 |
2009年 | 14篇 |
2008年 | 29篇 |
2007年 | 31篇 |
2006年 | 25篇 |
2005年 | 23篇 |
2004年 | 14篇 |
2003年 | 10篇 |
2002年 | 15篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 8篇 |
1992年 | 2篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1980年 | 2篇 |
1978年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 2篇 |
1967年 | 1篇 |
1966年 | 3篇 |
1965年 | 1篇 |
1961年 | 1篇 |
1924年 | 1篇 |
1919年 | 1篇 |
1918年 | 2篇 |
1917年 | 2篇 |
1916年 | 3篇 |
排序方式: 共有561条查询结果,搜索用时 31 毫秒
1.
2.
3.
Psychopathology in epilepsy 总被引:3,自引:0,他引:3
K R Perrine 《Seminars in neurology》1991,11(2):175-181
Although the majority of epileptics who are well controlled on medication do not show significant evidence of psychopathology, a subset of epileptics have serious psychiatric disturbances. Risk factors for the development of psychopathology appear to include poorly-controlled seizures, a long duration of seizure disorder with onset in childhood, seizure focus in the temporal lobe, bilateral or multiple discharges on EEG, and structural lesions. All of these factors appear to put the patient at greater risk of brain dysfunction, possibly because of the disruption of limbic functions associated with behavior and personality. The onset of seizures in childhood is likely to affect the development of personality and social functioning adversely. Although not a focus of this article, premorbid personality, psychologic reactions to having epilepsy, and the social problems accompanying the disease are likely to contribute greatly to the development of psychopathology. The development of psychiatric disorders in epilepsy thus appears to be a complex, multifactorial process. No single factor, such as seizure type, EEG findings, lateralization, pathology, or demographic variables is likely to be explanatory. Recent research has focused on accounting for many of these factors, and future investigations should shed further light on why some epileptics develop psychiatric problems and how best to treat these disorders. 相似文献
4.
Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. 总被引:4,自引:0,他引:4 下载免费PDF全文
S P Perrine A Rudolph D V Faller C Roman R A Cohen S J Chen Y W Kan 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(22):8540-8542
The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching. 相似文献
5.
A 22-nucleotide spliced leader sequence in the human parasitic nematode Brugia malayi is identical to the trans-spliced leader exon in Caenorhabditis elegans. 总被引:15,自引:5,他引:10 下载免费PDF全文
A M Takacs J A Denker K G Perrine P A Maroney T W Nilsen 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(21):7932-7936
The mRNAs encoding a 63-kDa antigen in the human parasitic nematode Brugia Malayi contain a spliced leader sequence of 22 nucleotides (nt) that is identical to the trans-spliced leader found on certain actin mRNAs in the distantly related nematode Caenorhabditis elegans. The 22-nt sequence does not appear to be encoded near the 63-kDa genes but is present in multiple copies in several locations within the parasite genome, including the 5S rRNA gene repeat. The 5S-linked copies of the 22-nt sequence are transcribed to yield a 109-nt nonpolyadenylated RNA with the 22-nt leader sequence at its 5' end. We suggest that the 22-nt leader is acquired by 63-kDa antigen mRNAs through trans-splicing. These results indicate that trans-splicing is widespread in nematodes and argue for the functional significance of the 22-nt spliced leader exon in nematode mRNA metabolism. 相似文献
6.
Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting. 总被引:1,自引:0,他引:1
Hervé Allain Stéphane Schück Fatima Nachit-Ouinekh Perrine Plouin Anne-Marie Brunon Jacques Boulliat Florence Mercier Alain Slama Michel Baulac Abdelkader El Hasnaoui 《Seizure》2007,16(2):173-184
Quality of life is impaired in patients with epilepsy and can be improved by effective therapy. Randomised clinical trials have shown that lamotrigine treatment is associated with improved quality of life. However, little information is available on quality of life or treatment effects in patients with epilepsy in the general population. The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting. The study included adult patients with epilepsy in whom lamotrigine therapy was initiated. Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life questionnaire at inclusion and at a follow-up visit in the next 4 months. Demographic information and medical history were provided by the investigator. These were evaluated as potential determinants of change in quality of life using logistic regression. Three hundred and forty-one patients were evaluated, 192 starting lamotrigine in combination with another drug, 90 as a first-line monotherapy, 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination. Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group. 34.6% of patients were considered to be responders, with no significant differences between treatment regimen. Most improvement was seen for the energy-fatigue and medication effects subscales and, for the first-line group, seizure worry. Seizure type was the only determinant of improvement of quality of life identified. In conclusion, lamotrigine treatment is associated with improved quality of life, regardless of treatment regimen. 相似文献
7.
Michael S. Boosalis Tohru Ikuta Betty S. Pace Silvana da Fonseca Gary L. White Douglas V. Faller Susan P. Perrine 《Blood cells, molecules & diseases》1997,23(3):434-442
ABSTRACT: Short-chain fatty acids, such as butyrate and propionate, induce fetal globin gene expression and are under clinical investigation in the β-hemoglobinopathies. Limitations of the short-chain fatty acids as therapeutics include their rapid metabolism and a tendency to induce cell growth arrest if administered for prolonged periods. In studies described here, the cellular effects of other inducers of fetal globin, phenoxyacetic acid and derivatives of short-chain fatty acids and cinnamic acids, were investigated in the human erythroid cell line K562, the IL-3 dependent multi-lineage cell line (32D), and in mice and primates. Several test compounds supported 32D cell proliferation despite a 50-fold depletion of IL-3, which resulted in growth arrest and apoptotic death in control cells. The degree of proliferation induced by certain test compounds was similar to the degree of proliferation induced by Erythropoietin and G-CSF in the cells. Eight of ten compounds induced γ globin mRNA in K562 cells. A 2.5 to 6-fold increase in reticulocytosis was observedin vivoin mice treated with two prototype compounds. Pharmacokinetic studies of three prototype compounds demonstrated millimolar plasma concentrations after single oral doses for many hours in primates. These findings identify orally bioavailable compounds which induce γ globin gene expression and hematopoietic cell proliferation through an activity which partially abrogates requirements for IL-3. Such compounds provide potential for oral therapeutics which stimulate proliferation of hematopoietic cells of multiple lineages, as well as inducing fetal globin. 相似文献
8.
Perrine Brunelle Anne‐Sophie Jourdain Fabienne Escande Jelena Martinovic Juliette Dupont Tiffany Busa Anne Moncla Frédéric Frénois Morgane Stichelbout Sylvie Manouvrier‐Hanu Florence Petit 《American journal of medical genetics. Part A》2019,179(7):1351-1356
Split‐hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb malformation typically limited to a defect of the central rays of the autopod, presenting as a median cleft of hands and feet. It can be associated with long bone deficiency or included in more complex syndromes. Among the numerous genetic causes, WNT10B homozygous variants have been recently identified in consanguineous families, but remain still rarely described (SHFM6; MIM225300). We report on three novel SHFM families harboring WNT10B variants and review the literature, allowing us to highlight some clinical findings. The feet are more severely affected than the hands and there is a frequent asymmetry without obvious side‐bias. Syndactyly of third–fourth fingers was a frequent finding (62%). Polydactyly, which was classically described in SHFM6, was only present in 27% of patients. No genotype–phenotype correlation is delineated but heterozygous individuals might have mild features of SHFM, suggesting a dose‐effect of the WNT10B loss‐of‐function. 相似文献
9.
10.