全文获取类型
收费全文 | 3027篇 |
免费 | 149篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 134篇 |
妇产科学 | 74篇 |
基础医学 | 404篇 |
口腔科学 | 34篇 |
临床医学 | 251篇 |
内科学 | 765篇 |
皮肤病学 | 71篇 |
神经病学 | 252篇 |
特种医学 | 55篇 |
外科学 | 376篇 |
综合类 | 6篇 |
一般理论 | 1篇 |
预防医学 | 113篇 |
眼科学 | 65篇 |
药学 | 166篇 |
中国医学 | 9篇 |
肿瘤学 | 405篇 |
出版年
2024年 | 2篇 |
2023年 | 18篇 |
2022年 | 35篇 |
2021年 | 53篇 |
2020年 | 46篇 |
2019年 | 56篇 |
2018年 | 75篇 |
2017年 | 54篇 |
2016年 | 50篇 |
2015年 | 79篇 |
2014年 | 113篇 |
2013年 | 105篇 |
2012年 | 187篇 |
2011年 | 200篇 |
2010年 | 131篇 |
2009年 | 124篇 |
2008年 | 202篇 |
2007年 | 204篇 |
2006年 | 196篇 |
2005年 | 193篇 |
2004年 | 197篇 |
2003年 | 181篇 |
2002年 | 174篇 |
2001年 | 56篇 |
2000年 | 31篇 |
1999年 | 38篇 |
1998年 | 31篇 |
1997年 | 37篇 |
1996年 | 37篇 |
1995年 | 30篇 |
1994年 | 20篇 |
1993年 | 16篇 |
1992年 | 21篇 |
1991年 | 19篇 |
1990年 | 20篇 |
1989年 | 25篇 |
1988年 | 19篇 |
1987年 | 15篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 12篇 |
1983年 | 5篇 |
1982年 | 13篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 6篇 |
1973年 | 2篇 |
排序方式: 共有3186条查询结果,搜索用时 15 毫秒
101.
102.
Carola Gianni Domenico G. Della Rocca Jun Kim Anu Sahore Salwan Andrea Natale Amin Al‐Ahmad 《Journal of cardiovascular electrophysiology》2020,31(8):2253-2256
A 72‐year‐old woman with a history of paroxysmal atrial fibrillation (AF) and sinus node dysfunction is seen in clinic for routine follow‐up. 相似文献
103.
Long‐term outcome in patients with ST segment elevation myocardial infarction and multivessel disease treated with culprit‐only,immediate, or staged multivessel percutaneous revascularization strategies: Insights from the REAL registry 下载免费PDF全文
104.
Acoustic emissions (AE) due to microcracking in solid materials permit the monitoring of fracture processes and the study of failure dynamics. As an alternative method of integrity assessment, measurements of electrical resistance can be used as well. In the literature, however, many studies connect the notion of criticality with AE originating from the fracture, but not with the changes in the electrical properties of materials. In order to further investigate the possible critical behavior of fracture processes in rocks and cement-based materials, we apply natural time (NT) analysis to the time series of AE and resistance measurements, recorded during fracture experiments on cement mortar (CM) and Luserna stone (LS) specimens. The NT analysis indicates that criticality in terms of electrical resistance changes systematically precedes AE criticality for all investigated specimens. The observed greater unpredictability of the CM fracture behavior with respect to LS could be ascribed to the different degree of material homogeneity, since LS (heterogeneous material) expectedly offers more abundant and more easily identifiable fracture precursors than CM (homogenous material). Non-uniqueness of the critical point by varying the detection threshold of cracking events is apparently due to finite size effects which introduce deviations from the self-similarity. 相似文献
105.
Laura Annaratone Enzo Medico Nelson Rangel Isabella Castellano Caterina Marchiò Anna Sapino Gianni Bussolati 《Endocrine pathology》2014,25(3):219-228
Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers. 相似文献
106.
Gianni Testino Patrizia Burra Ferruccio Bonino Francesco Piani Alessandro Sumberaz Roberto Peressutti Andrea Giannelli Castiglione Valentino Patussi Tiziana Fanucchi Ornella Ancarani Giovanna De Cerce Anna Teresa Iannini Giovanni Greco Antonio Mosti Marilena Durante Paola Babocci Mariano Quartini Davide Mioni Sarino Aricò Aniello Baselice Silvia Leone Fabiola Lozer Emanuele Scafato Paolo Borro 《World journal of gastroenterology : WJG》2014,20(40):14642-14651
Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. 相似文献
107.
Stefano Gianni Carlo Camilloni Rajanish Giri Angelo Toto Daniela Bonetti Angela Morrone Pietro Sormanni Maurizio Brunori Michele Vendruscolo 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(39):14141-14146
Folding and function may impose different requirements on the amino acid sequences of proteins, thus potentially giving rise to conflict. Such a conflict, or frustration, can result in the formation of partially misfolded intermediates that can compromise folding and promote aggregation. We investigate this phenomenon by studying frataxin, a protein whose normal function is to facilitate the formation of iron–sulfur clusters but whose mutations are associated with Friedreich’s ataxia. To characterize the folding pathway of this protein we carry out a Φ-value analysis and use the resulting structural information to determine the structure of the folding transition state, which we then validate by a second round of rationally designed mutagenesis. The analysis of the transition-state structure reveals that the regions involved in the folding process are highly aggregation-prone. By contrast, the regions that are functionally important are partially misfolded in the transition state but highly resistant to aggregation. Taken together, these results indicate that in frataxin the competition between folding and function creates the possibility of misfolding, and that to prevent aggregation the amino acid sequence of this protein is optimized to be highly resistant to aggregation in the regions involved in misfolding.Frustration is a general condition that arises in the presence of conflicting requirements. A system is frustrated when it is impossible to fully minimize its energy by optimizing simultaneously all of the possible interactions among its components (1). Although complex systems tend in general to exhibit frustration because of the large number and heterogeneity of their components, protein molecules are remarkable in that their folding process involves interactions that express a minimal level of frustration. According to the so-called principle of minimal frustration, the energy of proteins decreases as they explore conformations increasingly similar in structure to the native state (2). Consequently, the free energy landscape of proteins is characterized by the presence of a well-defined global minimum and very few other local minima, which are typically intermediate states along the folding pathway. This organization of conformational space normally ensures rapid and reliable folding (2–6).Proteins, however, have evolved not only to fold, but also to function. Because the evolutionary constraints that select for a given function may be in conflict with the folding process, it is possible that local frustration patterns may localize in specific regions of proteins, in particular in their active sites. Indeed, a statistical survey of different proteins has shown that frustrated interactions tend to cluster at binding sites and that such frustration decreases upon complex formation (7). Because frustration is associated with the presence of local minima in the free energy landscape, it is important to understand how proteins have evolved to minimize the possible effects associated with these local minima, which are likely to contain misfolded elements and thus to potentially give rise to aggregation.To address this question we studied frataxin, a mitochondrial protein that binds both Fe2+ and Fe3+ ions and forms a ternary complex with the two main components of the iron–sulfur cluster biogenesis machinery (8–11). This protein offers good opportunities for investigating the relationships between folding, misfolding, and disease. Indeed, its dysfunction is related to a neurodegenerative disease called Friedreich’s ataxia (12). Frataxin is also capable of binding different divalent and trivalent cations, whose recognition sites have been mapped (13). Furthermore, frataxin is involved in donating iron to ferrochelatease via direct interaction through an extended binding site involving some of the residues implicated in metal binding (14).We have previously shown that frataxin folds via a complex mechanism, which we described through a broad free energy barrier (15). This feature, which has been associated with frustration (16), allows the experimental characterization of both the early and late events of folding (16–19). In this work we explored the mechanistic details of the folding reaction of frataxin at residue-level resolution. This result was achieved by characterizing the structures of both the early and late events of folding using Φ-value analysis (20) and restrained molecular dynamics simulations (21). By analyzing the structures of the different states along the folding process we found an unexpected number of nonnative interactions that slow down folding and superpose with the highly frustrated regions, as detected by the frustratometer server (22). The nonnative regions, which display peculiar Φ values, either negative or greater than unity, were predicted on the basis of the transition state structures determined from the Φ values, and subsequently confirmed by a second round of amino acid substitutions rationally designed to probe misfolded regions along the folding pathway.The characterization of the folding pathway of frataxin and of its misfolded elements enables us to discuss the competition between folding and function and its consequences for misfolding and aggregation. 相似文献
108.
109.
110.
Gerlini G Di Gennaro P Mariotti G Urso C Chiarugi A Caporale R Pimpinelli N Borgognoni L 《Blood》2012,119(20):4807-8; author reply 4809-10