全文获取类型
收费全文 | 4244篇 |
免费 | 242篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 28篇 |
儿科学 | 131篇 |
妇产科学 | 92篇 |
基础医学 | 617篇 |
口腔科学 | 56篇 |
临床医学 | 352篇 |
内科学 | 818篇 |
皮肤病学 | 84篇 |
神经病学 | 523篇 |
特种医学 | 218篇 |
外科学 | 488篇 |
综合类 | 37篇 |
一般理论 | 1篇 |
预防医学 | 278篇 |
眼科学 | 253篇 |
药学 | 216篇 |
肿瘤学 | 307篇 |
出版年
2023年 | 30篇 |
2021年 | 71篇 |
2020年 | 70篇 |
2019年 | 64篇 |
2018年 | 87篇 |
2017年 | 66篇 |
2016年 | 116篇 |
2015年 | 109篇 |
2014年 | 131篇 |
2013年 | 164篇 |
2012年 | 266篇 |
2011年 | 306篇 |
2010年 | 140篇 |
2009年 | 154篇 |
2008年 | 207篇 |
2007年 | 180篇 |
2006年 | 186篇 |
2005年 | 162篇 |
2004年 | 128篇 |
2003年 | 148篇 |
2002年 | 158篇 |
2001年 | 114篇 |
2000年 | 105篇 |
1999年 | 81篇 |
1998年 | 37篇 |
1997年 | 45篇 |
1996年 | 26篇 |
1994年 | 23篇 |
1993年 | 24篇 |
1992年 | 54篇 |
1991年 | 52篇 |
1990年 | 59篇 |
1989年 | 63篇 |
1988年 | 43篇 |
1987年 | 46篇 |
1986年 | 61篇 |
1985年 | 41篇 |
1984年 | 36篇 |
1983年 | 25篇 |
1982年 | 29篇 |
1977年 | 21篇 |
1976年 | 23篇 |
1975年 | 25篇 |
1973年 | 36篇 |
1972年 | 28篇 |
1971年 | 26篇 |
1970年 | 31篇 |
1968年 | 26篇 |
1967年 | 26篇 |
1966年 | 20篇 |
排序方式: 共有4499条查询结果,搜索用时 31 毫秒
1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
2.
Elaine Haddock Greg Saturday Friederike Feldmann Patrick W. Hanley Atsushi Okumura Jamie Lovaglio Dan Long Tina Thomas Dana P. Scott Mikayla Pulliam Jürgen A. Richt Emmie de Wit Heinz Feldmann 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(2)
Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.Reston virus (RESTV) was discovered in 1989/1990 in macaques imported into the United States from the Philippines for research purposes (1). Since then, there have been several episodes of disease caused by RESTV in macaques and rare asymptomatic infections in humans (2, 3). Unexpectedly, in 2008, RESTV emerged in pigs in the Philippines, and, shortly thereafter, RESTV sequences were detected in Chinese swine, raising zoonotic and food safety concerns (4, 5). RESTV constitutes a separate species in the genus Ebolavirus, family Filoviridae, and is generally thought of as the human apathogenic filovirus (6). Aside from humans (2, 3), RESTV has been shown to naturally and experimentally infect macaques, swine, ferrets, bats, and several rodent species (4, 5, 7–13). Upon experimental infection, macaques and ferrets, as well as immunocompromised rodents, such as STAT-1 knockout mice, develop severe disease with lethal outcome, whereas immunocompetent rodents generally do not (9–12). Whether RESTV itself causes disease in naturally infected domestic pigs remains unknown, since the RESTV-infected pigs from the Philippines were coinfected with the virulent arterivirus porcine reproductive and respiratory syndrome virus (PRRSV; now Betaarterivirus suid 1). In an initial experimental study, domestic pigs infected with RESTV only exhibited subclinical infections with evidence for virus shedding (7). We studied RESTV infection in young (3- to 7-wk-old) Yorkshire cross pigs, a swine breed used frequently in commercial pig production systems around the world. The main objective was to determine an age-dependent susceptibility to infection. 相似文献
3.
Qianlai Luo Jonathan N. Hofmann Ruth M. Pfeiffer Cari M. Kitahara Minkyo Song Meredith S. Shiels 《International journal of cancer. Journal international du cancer》2023,153(1):64-72
In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend. 相似文献
4.
Lukas Frase Peter Selhausen Lukas Krone Sulamith Tsodor Friederike Jahn Bernd Feige Jonathan G. Maier Florian Mainberger Hannah Piosczyk Marion Kuhn Stefan Klöppel Annette Sterr Chiara Baglioni Kai Spiegelhalder Dieter Riemann Michael A. Nitsche Christoph Nissen 《Brain stimulation》2019,12(3):674-683
Background
Arousal and sleep represent basic domains of behavior, and alterations are of high clinical importance.Objective/hypothesis
The aim of this study was to further elucidate the neurobiology of insomnia disorder (ID) and the potential for new treatment developments, based on the modulation of cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS). Specifically, we tested the hypotheses that bi-frontal anodal tDCS shortens and cathodal tDCS prolongs total sleep time in patients with ID, compared to sham stimulation. Furthermore, we tested for differences in indices of arousal between ID patients and healthy controls and explored their potential impact on tDCS effects.Methods
Nineteen ID patients underwent a within-subject repeated-measures sleep laboratory study with adaptation, baseline and three experimental nights. Bifrontal anodal, cathodal and sham tDCS was delivered in a counterbalanced order immediately prior to sleep. Wake EEG was recorded prior to and after tDCS as well as on the following morning. Subsequently, we compared patients with ID to a healthy control group from an earlier dataset.Results
Against our hypothesis, we did not observe any tDCS effects on sleep continuity or sleep architecture in patients with ID. Further analyses of nights without stimulation demonstrated significantly increased levels of arousal in ID patients compared to healthy controls, as indexed by subjective reports, reduced total sleep time, increased wake after sleep onset and increased high frequency EEG power during wakefulness and NREM sleep. Of note, indices of increased arousal predicted the lack of effect of tDCS in ID patients.Conclusions
Our study characterizes for the first time differential effects of tDCS on sleep in patients with ID and healthy controls, presumably related to persistent hyperarousal in ID. These findings suggest that adapted tDCS protocols need to be developed to modulate arousal and sleep dependent on baseline arousal levels. 相似文献5.
Lino Möhrmann Martina K. Zowada Hendrik Strakerjahn Christine Siegl Annette Kopp-Schneider Damir Krunic Dirk Strunk Martin Schneider Mark Kriegsmann Katharina Kriegsmann Friederike Herbst Claudia R. Ball Hanno Glimm Sebastian M. Dieter 《International journal of cancer. Journal international du cancer》2020,147(2):519-531
Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity. 相似文献
6.
Ronald F. Pfeiffer 《Neurotherapeutics》2020,17(4):1464
Recognition of the importance of nonmotor dysfunction as a component of Parkinson’s disease has exploded over the past three decades. Autonomic dysfunction is a frequent and particularly important nonmotor feature because of the broad clinical spectrum it covers. Cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory abnormalities all can appear in the setting of Parkinson’s disease. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both patient and partner. Alterations in sweating and body temperature are not widely recognized but often are present. Autonomic dysfunction can significantly and deleteriously impact quality of life for individuals with Parkinson’s disease. Because effective treatment for many aspects of autonomic dysfunction is available, it is vitally important that assessment of autonomic dysfunction be a regular component of the neurologic history and exam and that appropriate treatment be initiated and maintained.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00897-4) contains supplementary material, which is available to authorized users.Key Words: Autonomic, gastrointestinal, orthostatic hypotension, urinary, erectile dysfunction, thermoregulatory 相似文献
7.
Kronenberg Golo Klempin Friederike 《European archives of psychiatry and clinical neuroscience》2020,270(4):497-498
European Archives of Psychiatry and Clinical Neuroscience - 相似文献
8.
Prof. Dr. Franz Pfeiffer 《Stomatologie》2015,112(7-8):323-324
9.
10.
Friederike Pfeiffer Gabriele Frommer‐Kaestle Petra Fallier‐Becker 《Brain pathology (Zurich, Switzerland)》2019,29(5):675-692
Multiple Sclerosis is an autoimmune disorder causing neurodegeneration mostly in young adults. Thereby, myelin is lost in the inflammatory lesions leaving unmyelinated axons at a high risk to degenerate. Oligodendrocyte precursor cells maintain their regenerative capacity into adulthood and are able to remyelinate axons if they are properly activated and differentiate. Neuronal activity influences the success of myelination indicating a close interplay between neurons and oligodendroglia. The myelination profile determines the distribution of voltage‐gated ion channels along the axon. Here, we analyze the distribution of the sodium channel subunit Nav1.6 and the ultrastructure of axons after cuprizone‐induced demyelination in transgenic mice expressing GFP in oligodendroglial cells. Using this mouse model, we found an increased number of GFP‐expressing oligodendroglial cells compared to untreated mice. Analyzing the axons, we found an increase in the number of nodes of Ranvier in mice that had received cuprizone. Furthermore, we found an enhanced portion of unmyelinated axons showing vesicles in the cytoplasm. These vesicles were labeled with VGlut1, indicating that they are involved in axonal signaling. Our results highlight the flexibility of axons towards changes in the glial compartment and depict the structural changes they undergo upon myelin removal. These findings might be considered if searching for new neuroprotective therapies that aim at blocking neuronal activity in order to avoid interfering with the process of remyelination. 相似文献