首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1128篇
  免费   104篇
  国内免费   79篇
  2023年   20篇
  2022年   30篇
  2021年   49篇
  2020年   44篇
  2019年   43篇
  2018年   35篇
  2017年   23篇
  2016年   44篇
  2015年   52篇
  2014年   79篇
  2013年   101篇
  2012年   102篇
  2011年   93篇
  2010年   60篇
  2009年   46篇
  2008年   55篇
  2007年   50篇
  2006年   51篇
  2005年   41篇
  2004年   27篇
  2003年   29篇
  2002年   17篇
  2001年   22篇
  2000年   15篇
  1999年   21篇
  1998年   12篇
  1997年   9篇
  1996年   9篇
  1995年   10篇
  1994年   3篇
  1993年   3篇
  1992年   10篇
  1991年   5篇
  1990年   5篇
  1989年   6篇
  1988年   6篇
  1987年   4篇
  1986年   9篇
  1985年   7篇
  1984年   6篇
  1982年   3篇
  1981年   4篇
  1979年   5篇
  1978年   3篇
  1977年   4篇
  1975年   3篇
  1972年   5篇
  1969年   4篇
  1968年   3篇
  1967年   4篇
排序方式: 共有1311条查询结果,搜索用时 31 毫秒
51.

Background

The world’s first reported patient infected with avian influenza H7N9 was treated at the Fifth People’s Hospital of Shanghai. Shortly thereafter, several other cases emerged in the local area. Here, we describe the detailed epidemiological and clinical data of 6 cases of avian influenza H7N9.

Methods and Findings

We analyzed the epidemiologic and clinical data from clustered patients infected with H7N9 in the Minhang District of Shanghai during a 2-week period. Of the 6 patients, 2 were from a single family. In addition, 3 patients had a history of contact with poultry; however, all 6 patients lived in the proximity of 2 food markets where the H7N9 virus was detected in chickens and pigeons. The main symptoms were fever, cough, and hemoptysis. At onset, a decreased lymphocyte count and elevated creatine kinase, lactate dehydrogenase, procalcitonin, and C-reactive protein levels were observed. As the disease progressed, most patients developed dyspnea and hypoxemia. Imaging studies revealed lung consolidation and multiple ground-glass opacities in the early stage, rapidly extending bilaterally. All patients were treated with oseltamivir tablets beginning on days 3–8 after onset. The main complications were as follows: acute respiratory distress syndrome (ARDS; 83.3%), secondary bacterial infection (66.7%), pleural effusion (50%), left ventricular failure (33.3%), neuropsychiatric symptoms (33.3%), and rhabdomyolysis (16.7%). Of the 6 patients, 4 died of ARDS, with 2 patients recovering from the infection.

Conclusions

An outbreak of H7N9 infection occurred in the Minhang District of Shanghai that easily progressed to acute respiratory distress syndrome. Two cases showed family aggregation, which led us to identify the H7N9 virus and indicated that human transmission may be involved in the spread of this infection.  相似文献   
52.

Background

Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity.

Methods

In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated.

Results

Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient −0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values.

Conclusions

Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.  相似文献   
53.
54.
Pirh2 is a p53 inducible gene that encodes a RING-H2 domain and is proposed to be a main regulator of p53 protein, thus fine tuning the DNA damage response. Pirh2 interacts physically with p53 and promotes its MDM2-independent ubiquitination and subsequent degradation as well as participates in an auto-regulatory feedback loop that controls p53 function. Pirh2 also self-ubiquitinates. Interestingly, Pirh2 is overexpressed in a wide range of human tumors. In this study, we investigated the domains and residues essential for Pirh2 self-ubiquitination. Deletions were made in each of the three major domains of Pirh2: the N-terminal domain (NTD), Ring domain (RING), and C-terminal domain (CTD). The effects of these deletions on Pirh2 self-ubiquitination were then assessed using in vitro ubiquitination assays. Our results demonstrate that the RING domain is essential, but not sufficient, for Pirh2 self-ubiquitination and that residues 240–250 of the C-terminal domain are also essential. Our results demonstrate that Pirh2 mediated p53 polyubiquitination occurs mainly through the K48 residue of ubiquitin in vitro. Our data further our understanding of the mechanism of Pirh2 self-ubiquitination and may help identify valuable therapeutic targets that play roles in reducing the effects of the overexpression of Pirh2, thus maximizing p53''s response to DNA damage.  相似文献   
55.
56.
Vasopressin neurons generate distinctive phasic patterned spike activity in response to elevated extracellular osmotic pressure. These spikes are generated in the cell body and are conducted down the axon to the axonal terminals where they trigger Ca2+ entry and subsequent exocytosis of hormone-containing vesicles and secretion of vasopressin. This mechanism is highly non-linear, subject to both frequency facilitation and fatigue, such that the rate of secretion depends on both the rate and patterning of the spike activity. Here we used computational modelling to investigate this relationship and how it shapes the overall response of the neuronal population. We generated a concise single compartment model of the secretion mechanism, fitted to experimentally observed profiles of facilitation and fatigue, and based on representations of the hypothesised underlying mechanisms. These mechanisms include spike broadening, Ca2+ channel inactivation, a Ca2+ sensitive K+ current, and releasable and reserve pools of vesicles. We coupled the secretion model to an existing integrate-and-fire based spiking model in order to study the secretion response to increasing synaptic input, and compared phasic and non-phasic spiking models to assess the functional value of the phasic spiking pattern. The secretory response of individual phasic cells is very non-linear, but the response of a heterogeneous population of phasic cells shows a much more linear response to increasing input, matching the linear response we observe experimentally, though in this respect, phasic cells have no apparent advantage over non-phasic cells. Another challenge for the cells is maintaining this linear response during chronic stimulation, and we show that the activity-dependent fatigue mechanism has a potentially useful function in helping to maintain secretion despite depletion of stores. Without this mechanism, secretion in response to a steady stimulus declines as the stored content declines.  相似文献   
57.
58.
59.
The NAD-dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX-resistant K562 cells (K562R) in a dose-dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX-induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX-induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase-3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.  相似文献   
60.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号