全文获取类型
收费全文 | 615篇 |
免费 | 26篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 28篇 |
妇产科学 | 14篇 |
基础医学 | 156篇 |
口腔科学 | 1篇 |
临床医学 | 36篇 |
内科学 | 68篇 |
皮肤病学 | 2篇 |
神经病学 | 45篇 |
特种医学 | 36篇 |
外科学 | 52篇 |
综合类 | 1篇 |
预防医学 | 20篇 |
眼科学 | 32篇 |
药学 | 33篇 |
肿瘤学 | 110篇 |
出版年
2022年 | 7篇 |
2021年 | 11篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 24篇 |
2012年 | 42篇 |
2011年 | 31篇 |
2010年 | 33篇 |
2009年 | 17篇 |
2008年 | 42篇 |
2007年 | 40篇 |
2006年 | 40篇 |
2005年 | 41篇 |
2004年 | 35篇 |
2003年 | 30篇 |
2002年 | 27篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 16篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 10篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有642条查询结果,搜索用时 0 毫秒
151.
Newman CJ Ziegler AL Jeannet PY Roulet-Perez E Deonna TW 《Developmental medicine and child neurology》2006,48(2):96-102
We report on seven children (five males, two females) who presented with marked, often asymmetrical, toe-walking from onset of independent walking, associated with abnormal foot postures and increased tone at the ankles with characteristics of dystonia. Most of the children had presented with unusual pre-walking locomotion and a mild delay in independent walking. They did not fit into the usual categories of 'habitual' toe-walking or congenital short tendo calcaneus but nor did they have the clinical signs of spastic diplegia or of a peripheral neuromuscular disease. Normalization occurred progressively in the second to fourth years of life. The children were re-examined several years later (1 to 11y) and were normal. We believe that their persistent toe-walking corresponded to a variant of 'transient focal dystonia of infancy'. Knowledge of its existence may justify a period of observation without special investigations, surgery, or casting. 相似文献
152.
153.
Abramowski D Wiederhold KH Furrer U Jaton AL Neuenschwander A Runser MJ Danner S Reichwald J Ammaturo D Staab D Stoeckli M Rueeger H Neumann U Staufenbiel M 《The Journal of pharmacology and experimental therapeutics》2008,327(2):411-424
Human beta-amyloid precursor protein (APP) transgenic mice are commonly used to test potential therapeutics for Alzheimer's disease. We have characterized the dynamics of beta-amyloid (Abeta) generation and deposition following gamma-secretase inhibition with compound LY-411575 [N(2)-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N(1)-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide]. Kinetic studies in preplaque mice distinguished a detergent-soluble Abeta pool in brain with rapid turnover (half-lives for Abeta40 and Abeta42 were 0.7 and 1.7 h) and a much more stable, less soluble pool. Abeta in cerebrospinal fluid (CSF) reflected the changes in the soluble brain Abeta pool, whereas plasma Abeta turned over more rapidly. In brain, APP C-terminal fragments (CTF) accumulated differentially. The half-lives for gamma-secretase degradation were estimated as 0.4 and 0.1 h for C99 and C83, respectively. Three different APP transgenic lines responded very similarly to gamma-secretase inhibition regardless of the familial Alzheimer's disease mutations in APP. Amyloid deposition started with Abeta42, whereas Abeta38 and Abeta40 continued to turn over. Chronic gamma-secretase inhibition lowered amyloid plaque formation to a different degree in different brain regions of the same mice. The extent was inversely related to the initial amyloid load in the region analyzed. No evidence for plaque removal below baseline was obtained. gamma-Secretase inhibition led to a redistribution of intracellular Abeta and an elevation of CTFs in neuronal fibers. In CSF, Abeta showed a similar turnover as in preplaque animals demonstrating its suitability as marker of newly generated, soluble Abeta in plaque-bearing brain. This study supports the use of APP transgenic mice as translational models to characterize Abeta-lowering therapeutics. 相似文献
154.
Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes 下载免费PDF全文
Nordgard SH Johansen FE Alnaes GI Naume B Børresen-Dale AL Kristensen VN 《Breast cancer research : BCR》2007,9(6):113-2
Recently, genome-wide association studies of breast cancer revealed single nucleotide polymorphisms (SNPs) in five genes with novel association to susceptibility. While there is little doubt that the novel susceptibility markers produced from such highly powered studies are true, the mechanisms by which they cause the susceptibility remain undetermined. We have looked at the expression levels of the identified genes in tumours and found that they are highly significantly differentially expressed between the five established breast cancer subtypes. Also, a significant association between SNPs in these genes and their expression in tumours was seen as well as a significantly different frequency of the SNPs between the subtypes. This suggests that the observed genes are associated with different breast cancer subtypes, and may exert their effect through their expression in the tumours. Thus, future studies stratifying patients by their molecular subtypes may give much more power to classic case control studies, and genes of no or borderline significance may appear to be high-penetrant for certain subtypes and, therefore, be identifiable. 相似文献
155.
Janos Papp Marietta Eva Kovacs Szilvia Solyom Miklos Kasler Anne-Lise Børresen-Dale Edith Olah 《BMC medical genetics》2010,11(1):169
Background
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11/LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11/LKB1 and their association to disease phenotype. 相似文献156.
Arlettaz A Collomp K Portier H Lecoq AM Pelle A de Ceaurriz J 《International journal of sports medicine》2006,27(9):673-679
To study the effects of a therapeutical dose of corticosteroid alone or associated with beta-2 agonist on performance and substrate response during intense submaximal exercise, seven healthy moderately trained male volunteers participated in the double-blind randomized cross-over study. An intense endurance exercise test to exhaustion was performed after ingestion of placebo (Pla), 20 mg prednisolone (Pred), and 20 mg prednisolone plus 4 mg salbutamol (Pred-Sal). Blood samples were collected at rest, after 5, 10 min of exercise, at exhaustion, and after 5 (r5), 10 (r10), and 20 (r20) min of passive recovery for ACTH, growth hormone, insulin, blood glucose, and lactate measurements. There were no significant differences in exercise time to exhaustion between the three treatments (Pla: 21.5 +/- 2.9; Pred: 22.0 +/- 2.5; Pred-Sal: 24.2 +/- 2.8 min). ACTH was significantly lowered after Pred and Pred-Sal vs. Pla from the start of exercise to the end of the experiment (p < 0.05). Pred and Pred-Sal increased resting and recovery (r10 and r20) significantly but not exercise blood glucose values. There were no significant differences in growth hormone concentrations between the three treatments whereas insulin was significantly higher at rest, during exercise, and at r20 after Pred-Sal administration vs. Pred and Pla (p < 0.05). Pred and Pred-Sal showed no significant effect on blood lactate compared with Pla treatment. These preliminary results do not support the hypothesis that acute oral therapeutic corticosteroid intake alone or associated with beta-2 mimetic improves performance during intense submaximal exercise, but further studies are necessary with tests of longer duration. 相似文献
157.
Pascal Belin Marie Hélène Le Du Alistair Fielding Olivier Lequin Micka?l Jacquet Jean-Baptiste Charbonnier Alain Lecoq Robert Thai Marie Cour?on Cédric Masson Christophe Dugave Roger Genet Jean-Luc Pernodet Muriel Gondry 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(18):7426-7431
The gene encoding the cytochrome P450 CYP121 is essential for Mycobacterium tuberculosis. However, the CYP121 catalytic activity remains unknown. Here, we show that the cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) binds to CYP121, and is efficiently converted into a single major product in a CYP121 activity assay containing spinach ferredoxin and ferredoxin reductase. NMR spectroscopy analysis of the reaction product shows that CYP121 catalyzes the formation of an intramolecular C-C bond between 2 tyrosyl carbon atoms of cYY resulting in a novel chemical entity. The X-ray structure of cYY-bound CYP121, solved at high resolution (1.4 Å), reveals one cYY molecule with full occupancy in the large active site cavity. One cYY tyrosyl approaches the heme and establishes a specific H-bonding network with Ser-237, Gln-385, Arg-386, and 3 water molecules, including the sixth iron ligand. These observations are consistent with low temperature EPR spectra of cYY-bound CYP121 showing a change in the heme environment with the persistence of the sixth heme iron ligand. As the carbon atoms involved in the final C-C coupling are located 5.4 Å apart according to the CYP121-cYY complex crystal structure, we propose that C-C coupling is concomitant with substrate tyrosyl movements. This study provides insight into the catalytic activity, mechanism, and biological function of CYP121. Also, it provides clues for rational design of putative CYP121 substrate-based antimycobacterial agents. 相似文献
158.
Franca Podo Lutgarde M.C. Buydens Hadassa Degani Riet Hilhorst Edda Klipp Ingrid S. Gribbestad Sabine Van Huffel Hanneke W.M. van Laarhoven Jan Luts Daniel Monleon Geert J. Postma Nicole Schneiderhan-Marra Filippo Santoro Hans Wouters Hege G. Russnes Therese Sørlie Elda Tagliabue Anne-Lise Børresen-Dale 《Molecular oncology》2010,4(3):209-229
Triple‐negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial response to chemotherapy and present lack of clinically established targeted therapies. Advances in the design of individualized strategies for treatment of TNBC patients require further elucidation, by combined ‘omics’ approaches, of the molecular mechanisms underlying TNBC phenotypic heterogeneity, and the still poorly understood association of TNBC with BRCA1 mutations. An overview is here presented on TNBC profiling in terms of expression signatures, within the functional genomic breast tumor classification, and ongoing efforts toward identification of new therapy targets and bioimaging markers. Due to the complexity of aberrant molecular patterns involved in expression, pathological progression and biological/clinical heterogeneity, the search for novel TNBC biomarkers and therapy targets requires collection of multi‐dimensional data sets, use of robust multivariate data analysis techniques and development of innovative systems biology approaches. 相似文献
159.
160.
Margaret Chitemerere Tone Ikdahl Andersen Ruth Holm Frank Karlsen Anne-Lise Børresen Jahn Marthin Nesland 《Breast cancer research and treatment》1996,41(2):103-109
Summary Abnormalities in theTP53 tumour suppressor gene in 75 atypical ductal hyperplasias and 62 ductalcarcinomasin situ (DCIS) of the breast were studied using immunohistochemistry and mutation analysis. Accumulation of p53 protein was detected in 10 out of 62 (16%) DCIS, whereas no cases of positive staining was observed in the atypical lesions.TP53 mutations were identified in four out of 30 (13%) DCIS by constant denaturant gel electrophoresis (CDGE). Two of these cases were positive and two negative for p53 protein. A total of 12 out of 62 DCIS (19%) carriedTP53 mutation and/or p53 protein overexpression. The present results suggest thatTP53 alterations may be important in the development of a subset of DCIS. 相似文献