全文获取类型
收费全文 | 1282篇 |
免费 | 95篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 13篇 |
妇产科学 | 16篇 |
基础医学 | 217篇 |
口腔科学 | 108篇 |
临床医学 | 157篇 |
内科学 | 290篇 |
皮肤病学 | 11篇 |
神经病学 | 99篇 |
特种医学 | 43篇 |
外科学 | 188篇 |
综合类 | 6篇 |
一般理论 | 1篇 |
预防医学 | 63篇 |
眼科学 | 7篇 |
药学 | 80篇 |
中国医学 | 3篇 |
肿瘤学 | 66篇 |
出版年
2023年 | 6篇 |
2022年 | 29篇 |
2021年 | 46篇 |
2020年 | 25篇 |
2019年 | 45篇 |
2018年 | 44篇 |
2017年 | 16篇 |
2016年 | 32篇 |
2015年 | 36篇 |
2014年 | 53篇 |
2013年 | 66篇 |
2012年 | 93篇 |
2011年 | 108篇 |
2010年 | 59篇 |
2009年 | 46篇 |
2008年 | 97篇 |
2007年 | 91篇 |
2006年 | 91篇 |
2005年 | 80篇 |
2004年 | 69篇 |
2003年 | 61篇 |
2002年 | 44篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 13篇 |
1997年 | 8篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1383条查询结果,搜索用时 125 毫秒
31.
Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration
下载免费PDF全文
![点击此处可从《Blood》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Khandoga A Kessler JS Meissner H Hanschen M Corada M Motoike T Enders G Dejana E Krombach F 《Blood》2005,106(2):725-733
The endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. We investigated the role of junctional adhesion molecule-A (JAM-A), a receptor expressed in endothelial tight junctions, leukocytes, and platelets, for leukocyte transmigration during hepatic ischemia-reperfusion (I/R) in vivo. We show that JAM-A is up-regulated in hepatic venular endothelium during reperfusion. I/R-induced neutrophil transmigration was attenuated in both JAM-A-/- and endothelial JAM-A-/- mice as well as in mice treated with an anti-JAM-A antibody, whereas transmigration of T cells was JAM-A independent. Postischemic leukocyte rolling remained unaffected in JAM-A-/- and endothelial JAM-A-/- mice, whereas intravascular leukocyte adherence was increased. The extent of interactions of JAM-A-/- platelets with the postischemic endothelium was comparable with that of JAM-A+/+ platelets. The I/R-induced increase in the activity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and sinusoidal perfusion failure was not reduced in JAM-A-/- mice, while the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive hepatocytes was significantly higher. Thus, we show for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion, or platelet-endothelial cell interactions. JAM-A deficiency does not reduce I/R-induced microvascular and hepatocellular necrotic injury, but increases hepatocyte apoptosis, despite attenuation of neutrophil infiltration. 相似文献
32.
Lidbury BA Rulli NE Suhrbier A Smith PN McColl SR Cunningham AL Tarkowski A van Rooijen N Fraser RJ Mahalingam S 《The Journal of infectious diseases》2008,197(11):1585-1593
Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimics RRV disease in humans, we showed that macrophage-derived factors are critical in the development of striated muscle and joint tissue damage. Histologic analyses of muscle and ankle joint tissues demonstrated a substantial reduction in inflammatory infiltrates in infected mice depleted of macrophages (i.e., "macrophage-depleted mice"). Levels of the proinflammatory factors tumor necrosis factor-alpha, interferon-gamma, and macrophage chemoattractant protein-1 were also dramatically reduced in tissue samples obtained from infected macrophage-depleted mice, compared with samples obtained from infected mice without macrophage depletion. These factors were also detected in the synovial fluid of patients with RRV-induced polyarthritis. Neutralization of these factors reduced the severity of disease in mice, whereas blocking nuclear factor kappaB by treatment with sulfasalazine ameliorated RRV inflammatory disease and tissue damage. To our knowledge, these findings are the first to demonstrate that macrophage-derived products play important roles in the development of arthritis and myositis triggered by alphavirus infection. 相似文献
33.
34.
Roderick M. Card Muriel Mafura Theresa Hunt Miranda Kirchner Jan Weile Mamun-Ur Rashid Andrej Weintraub Carl Erik Nord Muna F. Anjum 《Antimicrobial agents and chemotherapy》2015,59(8):4410-4416
The aim of this study was to assess the impact of ciprofloxacin, clindamycin, and placebo administration on culturable Gram-negative isolates and the antibiotic resistance genes they harbor. Saliva and fecal samples were collected from healthy human volunteers before and at intervals, up to 1 year after antibiotic administration. Samples were plated on selective and nonselective media to monitor changes in different colony types or bacterial species. Following ciprofloxacin administration, there was a decrease of Escherichia coli in feces and after clindamycin administration a decrease of Bacteroides in feces and Leptotrichia in saliva, which all returned to pretreatment levels within 1 to 4 months. Ciprofloxacin administration also resulted in an increase in ciprofloxacin-resistant Veillonella in saliva, which persisted for 12 months. Additionally, 949 aerobic and anaerobic isolates purified from ciprofloxacin- and clindamycin-containing plates were screened for the presence of resistance genes. Resistance gene carriage was widespread in isolates from all three treatment groups, and no association was observed between genes and antibiotic administration. Although the anaerobic component of the microbiota was not a major reservoir of aerobe-associated antimicrobial resistance (AMR) genes, we detected the sulfonamide resistance gene sul2 in anaerobic isolates. The longitudinal nature of the study allowed identification of distinct Escherichia coli clones harboring multiple resistance genes, including one carrying an extended-spectrum β-lactamase blaCTX-M group 9 gene, which persisted in the gut for up to 4 months. This study provided insight into the effects of antibiotic administration on healthy microbiota and the diversity of resistance genes harbored therein. 相似文献
35.
Nancy Cardinez Leif E. Lovblom Johnny-Wei Bai Evan Lewis Alon Abraham Daniel Scarr Julie A. Lovshin Yuliya Lytvyn Genevieve Boulet Mohammed A. Farooqi Andrej Orszag Alanna Weisman Hillary A. Keenan Michael H. Brent Narinder Paul Vera Bril David Z. Cherney Bruce A. Perkins 《Journal of diabetes and its complications》2018,32(7):660-664
Aim
Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.Methods
Canadians with ≥50?years of T1D (n?=?361) completed health history questionnaires that included assessment of neuropathy (defined by Michigan Neuropathy Screening Instrument questionnaire components ≥3; NEUROPATHYMNSI-Q) and neuropathic pain. Multivariable logistic regression was used to determine sex-differences in neuropathic pain controlling for neuropathy.Results
Participants had mean age 66?±?9?years, median diabetes duration 53[51,58] years, mean HbA1c 7.5?±?1.0%, and 207(57%) were female. Neuropathic pain was present in 128(36%) of all participants, more prevalent among those with NEUROPATHYMNSI-Q compared to those without [96(63%) vs. 31(15%), p?<?0.001], and more prevalent in females compared to males [87(42%) vs. 41(27%), p?=?0.003]. Independent of the presence of NEUROPATHYMNSI-Q and other factors, female sex was associated with the presence of neuropathic pain [OR 2.68 (95% CI 1.4–5.0), p?=?0.002].Conclusions
We demonstrated a novel sex-specific difference in neuropathic pain in females compared to males with longstanding T1D, independent of the presence of neuropathy. Further research using more objective measures of neuropathy than the MNSI is justified to further understand this sex-specific difference. 相似文献36.
We review the impact of mitochondrial DNA (mtDNA) maintenance and mitochondrial function on the aging process. Mitochondrial function and mtDNA integrity are closely related. In order to create a protective barrier against reactive oxygen and nitrogen species (RONS) attacks and ensure mtDNA integrity, multiple cellular mtDNA copies are packaged together with various proteins in nucleoids. Regulation of antioxidant and RONS balance, DNA base excision repair, and selective degradation of damaged mtDNA copies preserves normal mtDNA quantities. Oxidative damage to mtDNA molecules does not substantially contribute to increased mtDNA mutation frequency; rather, mtDNA replication errors of DNA PolG are the main source of mtDNA mutations. Mitochondrial turnover is the major contributor to maintenance of mtDNA and functionally active mitochondria. Mitochondrial turnover involves mitochondrial biogenesis, mitochondrial dynamics, and selective autophagic removal of dysfunctional mitochondria (i.e., mitophagy). All of these processes exhibit decreased activity during aging and fall under greater nuclear genome control, possibly coincident with the emergence of nuclear genome instability. We suggest that the age-dependent accumulation of mutated mtDNA copies and dysfunctional mitochondria is associated primarily with decreased cellular autophagic and mitophagic activity. 相似文献
37.
Rafaële J.C. Huntjens Marleen M. Rijkeboer Andrej Krakau Peter J. de Jong 《Journal of behavior therapy and experimental psychiatry》2014
Background and objectives
Low trait self-control constitutes a core criterion in various psychiatric disorders. Personality traits such as low self-control are mostly indexed by self-report measures. However, several theorists emphasized the importance of differentiating between explicit and implicit indices of personality traits, Therefore, the present study examined the unique predictive validity of an implicit measure of trait self-control for spontaneous dysfunctional behavior.Methods
As a measure of implicit trait self-control, we used an irrelevant feature task: a speeded reaction time task comprising a task-relevant stimulus feature (i.e., capital vs. lower case letter type) and a task-irrelevant feature (high vs. low self-control word type). The irrelevant feature had to be ignored, while participants (n = 34) responded to the relevant stimulus feature. However, their response was either congruent or incongruent with the irrelevant stimulus feature, resulting in facilitated or deteriorated task performance. As indicators of trait-related spontaneous dysfunctional behavior, we included indices of frustration tolerance and the preference for short-term reward over meeting long-term goals. We also included two explicit measures of trait self-control: a self-report questionnaire and an explicit self-relevance rating of the implicit task stimuli.Results
Specifically the implicit measure of trait self-control showed predictive validity for the target self-control behaviors.Limitations
The predictive validity of implicit measures of personality traits requires further study in larger, non-student samples.Conclusions
As predicted, the implicit measure of trait self-control showed superior predictive power for spontaneous trait-related behavior. This finding points to the relevance of complementing the routinely used self-report measures with implicit measures of trait self-control. 相似文献38.
We can define the concept of mental health not just as a health phenomenon, but also as a social and psychological one. Defining mental health separately from mental illness places it into the concept of public health, which exceeds the medical definition of the determination of a "mental illness." The anthropology of health defines the medical treatment as a social practice, which takes into consideration a person's social context, the differences between genders, and the connection between personal and social. It accents the characteristics of social systems, values, and manifestations of social crises through basic concepts and discourses, such as gender and culture. Besides the consideration of health and disease, it also enables the consideration of a person in a highly industrialized society and of a culture as a totality. The phenomenon of destructive ways of manifesting psychic crises (within the presented case study research) implies that mental health should be seen as a social problem. 相似文献
39.
The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together 总被引:2,自引:0,他引:2
Pathare GR Nagy I Bohn S Unverdorben P Hubert A Körner R Nickell S Lasker K Sali A Tamura T Nishioka T Förster F Baumeister W Bracher A 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(1):149-154
Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP. 相似文献
40.
Andrej Petri? Scott A. Johnson Hung V. Pham Ying Li Simon ?eh Amalija Golobi? Eric D. Agdeppa Gerald Timbol Jie Liu Gyochang Keum Nagichettiar Satyamurthy Vladimir Kepe Kendall N. Houk Jorge R. Barrio 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(41):16492-16497
The positron-emission tomography (PET) probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the noninvasive brain imaging of amyloid-β (Aβ) and other amyloid aggregates present in Alzheimer’s disease and other neurodegenerative diseases. A series of FDDNP analogs has been synthesized and characterized using spectroscopic and computational methods. The binding affinities of these molecules have been measured experimentally and explained through the use of a computational model. The analogs were created by systematically modifying the donor and the acceptor sides of FDDNP to learn the structural requirements for optimal binding to Aβ aggregates. FDDNP and its analogs are neutral, environmentally sensitive, fluorescent molecules with high dipole moments, as evidenced by their spectroscopic properties and dipole moment calculations. The preferred solution-state conformation of these compounds is directly related to the binding affinities. The extreme cases were a nonplanar analog t-butyl-FDDNP, which shows low binding affinity for Aβ aggregates (520 nM Ki) in vitro and a nearly planar tricyclic analog cDDNP, which displayed the highest binding affinity (10 pM Ki). Using a previously published X-ray crystallographic model of 1,1-dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an amyloidogenic Aβ peptide model, we show that the binding affinity is inversely related to the distortion energy necessary to avoid steric clashes along the internal surface of the binding channel. 相似文献