全文获取类型
收费全文 | 264篇 |
免费 | 5篇 |
专业分类
耳鼻咽喉 | 3篇 |
妇产科学 | 4篇 |
基础医学 | 31篇 |
口腔科学 | 4篇 |
临床医学 | 19篇 |
内科学 | 23篇 |
皮肤病学 | 1篇 |
神经病学 | 26篇 |
特种医学 | 99篇 |
外科学 | 15篇 |
预防医学 | 12篇 |
眼科学 | 1篇 |
药学 | 16篇 |
肿瘤学 | 15篇 |
出版年
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2014年 | 6篇 |
2013年 | 11篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 7篇 |
2009年 | 8篇 |
2008年 | 10篇 |
2007年 | 13篇 |
2006年 | 19篇 |
2005年 | 8篇 |
2004年 | 6篇 |
2003年 | 14篇 |
2002年 | 6篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1967年 | 2篇 |
1964年 | 1篇 |
1959年 | 1篇 |
1907年 | 1篇 |
排序方式: 共有269条查询结果,搜索用时 265 毫秒
1.
Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes 总被引:17,自引:8,他引:17
Campuzano V; Montermini L; Lutz Y; Cova L; Hindelang C; Jiralerspong S; Trottier Y; Kish SJ; Faucheux B; Trouillas P; Authier FJ; Durr A; Mandel JL; Vescovi A; Pandolfo M; Koenig M 《Human molecular genetics》1997,6(11):1771-1780
Friedreich ataxia is a progressive neurodegenerative disorder caused by
loss of function mutations in the frataxin gene. In order to unravel
frataxin function we developed monoclonal antibodies raised against
different regions of the protein. These antibodies detect a processed 18
kDa protein in various human and mouse tissues and cell lines that is
severely reduced in Friedreich ataxia patients. By immunocytofluorescence
and immunocytoelectron microscopy we show that frataxin is located in
mitochondria, associated with the mitochondrial membranes and crests.
Analysis of cellular localization of various truncated forms of frataxin
expressed in cultured cells and evidence of removal of an N-terminal
epitope during protein maturation demonstrated that the mitochondrial
targetting sequence is encoded by the first 20 amino acids. Given the
shared clinical features between Friedreich ataxia, vitamin E deficiency
and some mitochondriopathies, our data suggest that a reduction in frataxin
results in oxidative damage.
相似文献
2.
Cova L Ratti A Volta M Fogh I Cardin V Corbo M Silani V 《Stem cells and development》2004,13(1):121-131
In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward. 相似文献
3.
Summary Two hundreds and sixty red foxes, eighteen badgers and eight stone martens from north-eastern Italy were examined for zoonotic
parasites by SCT, with particular attention to Trichinella sp. and Echinococcus multilocularis. No adult worms of E. multilocularis were observed in the intestine of red foxes or mustelids. Out of 223 fox faecal samples analysed by a commercial CA-ELISA,
5.8 % was positive to Echinococcus coproantigens. Trichinella sp. was detected by digestion of muscle in 1.2 % of examined foxes (2/172), but not in mustelids (0/11). Toxocara canis, responsible for human toxocarosis, resulted to be common in fox population (48.5 %). This parasite was found both in young
(53.3 % of cubs and 61.9 % of sub-adults) and in adult animals (42.7 %). Other zoonotic parasites as Uncinaria stenocephala (52.3 %) and Trichuris vulpis (0.4 %) were detected in fox populations. 相似文献
4.
Guareschi S Cova E Cereda C Ceroni M Donetti E Bosco DA Trotti D Pasinelli P 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(13):5074-5079
Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients' lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1. 相似文献
5.
Steckman DA Schneider PM Schuller JL Aleong RG Nguyen DT Sinagra G Vitrella G Brun F Cova MA Pagnan L Mestroni L Varosy PD Sauer WH 《The American journal of cardiology》2012,110(4):575-579
Some patients diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) are eventually found to have cardiac sarcoidosis (CS). Accurate differentiation between these 2 conditions has implications for immunosuppressive therapy and familial screening. We sought to determine whether cardiac magnetic resonance imaging (MRI) could be used to identify the characteristic findings to accurately differentiate between CS and ARVC. Consecutive patients with a diagnostic MRI scan indicating CS and/or ARVC constituted the cohort. All patients diagnosed with CS had histologic confirmation of sarcoidosis, and all patients with ARVC met the diagnostic task force criteria. The cardiac MRI data were retrospectively analyzed to identify possible differentiating characteristics. Of the patients, 40 had CS and 21 had ARVC. Those with CS were older and had more left ventricular scar. The presence of mediastinal lymphadenopathy or left ventricular septal involvement was seen exclusively in the patients with CS (p <0.001). A family history of sudden cardiac death was seen only in the ARVC group (p = 0.012). The right ventricular ejection fraction and ventricular volumes were also significantly different between the 2 groups. In conclusion, patients with CS have significantly different cardiac MRI characteristics than patients with ARVC. The cardiac volume, in addition to the degree and location of cardiac involvement, can be used to distinguish between these 2 disease entities. The presence of mediastinal lymphadenopathy and left ventricular septal scar favors a diagnosis of CS and not ARVC. Consideration of CS should be given if these MRI findings are observed during the evaluation for possible ARVC. 相似文献
6.
Carl F. Craver Florian Cova Leonard Green Joel Myerson R. Shayna Rosenbaum Donna Kwan Sacha Bourgeois‐Gironde 《Hippocampus》2014,24(11):1375-1380
The capacity to anticipate future experiences of regret has been hypothesized to explain otherwise irrational aspects of human decision‐making, including the certainty effect (Kahneman and Tversky (1979) Econometrica 47:263–291) and the common ratio effect (Allais (1953) Econometrica 21:503–546). The anticipated regret hypothesis predicts that individuals incapable of episodically imagining their personal futures, as has been reported for people with extensive damage to medial temporal lobe structures and resulting deficits in episodic thought, should be immune to these effects. We report that K.C., who has extensive bilateral damage to his hippocampus and adjacent medial temporal lobe structures and nearly complete deficits in his ability to episodically imagine his personal future, nonetheless displays both the certainty and the common ratio effects. These results suggest that the episodic anticipation of future regret does not explain the general human tendency to display the certainty and common ratio effects. © 2014 Wiley Periodicals, Inc. 相似文献
7.
Bertolotto Michele Campo Irene Sachs Camilla Ciabattoni Riccardo Bucci Stefano Cova Maria Assunta Van Nieuwenhove Sandy 《Abdominal imaging》2020,45(7):1973-1989
Abdominal Radiology - Erectile dysfunction (ED) is defined as the persistent inability to achieve and/or maintain an erection for a satisfactory sexual activity. It is secondary to several organic,... 相似文献
8.
H Tsukamoto Y S Kang L C Jones M Cova C J Herold E McVeigh D S Hungerford E A Zerhouni 《Investigative radiology》1992,27(4):275-281
RATIONALE AND OBJECTIVES. There is a continuing need for a greater sensitivity of magnetic resonance imaging (MRI) in the diagnosis of avascular necrosis (AVN). Previously, it was demonstrated that a dynamic MRI method, with gadolinium-DTPA (Gd-DTPA) enhancement, can detect acute changes not seen on spin-echo images after arterial occlusion in a dog model. Because venous congestion appears to be a more directly relevant hemodynamic abnormality in a majority of clinical AVN cases, the authors extended the dynamic MRI technique to study changes in venous occlusion. METHODS. Dynamic MRI of the proximal femur was performed in five adult dogs before and after unilateral ligation of common iliac and lateral circumflex veins. Sixteen sequential gradient-recalled pulse sequence (GRASS) images (time resolution = 45 mseconds, echo time = 9 mseconds, flip angle = 65 degrees) were obtained immediately after a bolus intravenous injection of 0.2 mmol/kg of Gd-DTPA. Simultaneous measurements of regional blood flow were made using the radioactive microsphere method. RESULTS. After venous ligation, there was a 25% to 45% decrease in the degree of enhancement compared with preligation values on the ligated side. The decrease in cumulative enhancement (integrated over the entire time course) was statistically significant. The occlusion technique was verified by confirming a statistically significant decrease in blood flow determined by the microsphere method. CONCLUSIONS. Dynamic Gd-DTPA-enhanced fast MRI technique can detect acute changes in bone marrow perfusion due to venous occlusion. This technique may have applications in the early detection of nontraumatic AVN. 相似文献
9.
Duflot A.; Hollstein M.; Mehrotra R.; Trepo C.; Montesano R.; Cova L. 《Carcinogenesis》1994,15(7):1353-1357
Dietary aflatoxin and hepatitis B virus infection may play arole in generating the p53 tumor suppressor gene codon 249 hotspotmutation found in human hepatocellular carcinomas (HCCs) fromQidong (China) and southern Africa. No data are available onthe HCC site-specific mutation of the p53 gene in hepadnavirus-infectedanimals exposed to AFB1. We have searched for the presence ofp53 gene codon 249 mutations in both duck hepatitis B virus(DHBV) positive and negative HCCs of domestic ducks from Qidong,where the human p53 hotspot is so prevalent, as well as in duckHCCs experimentally induced by AFB1. Direct sequencing of DNAamplification products encompassing p53 codon 249 did not revealany mutations in 11 HCCs from Qidongducks, regardless of thestatus of DHBV infection. In addition no mutation was detectedin four HCCs from AFB1-treated ducks. This contrasts with thehuman data; however, in humans, the mutation and the preferentialbinding of AFB1 to codon 249 occurs at the third nucleotideG, while in duck, the codon 249 lacks this G residue. The DNAsequence of adjacent codons is also different in the two specieseven though the amino acid sequence is identical. This may explainthe low frequency of mutation we have observed. In addition,species differences in metabolism and DNA repair could influencethe occurrence of codon 249 mutations. 相似文献
10.
The plasma levels, the urinary excretion and the biliary excretion of piperidinoethyl-3-methylflavone-8-carboxylate (flavoxate, F) were studied in rats after i.v. and after oral administration. Parallel experiments were made with 3-methyl-flavone-8-carboxylic acid (M), the main metabolite of F. The substances are found in blood and are excreted in the urine and in the bile. The quantities excreted in the urine after oral administration are similar to those excreted after i.v. administration, showing that the enteric availability of the drugs is almost complete. The end product in urine and in bile is represented by a substance which yields M after a strong acid hydrolysis. There are marked pharmacokinetic differences between F and M, probably related to their physical properties. 相似文献