全文获取类型
收费全文 | 1467篇 |
免费 | 103篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 60篇 |
妇产科学 | 31篇 |
基础医学 | 152篇 |
口腔科学 | 19篇 |
临床医学 | 166篇 |
内科学 | 326篇 |
皮肤病学 | 40篇 |
神经病学 | 134篇 |
特种医学 | 17篇 |
外科学 | 225篇 |
综合类 | 9篇 |
一般理论 | 7篇 |
预防医学 | 174篇 |
眼科学 | 43篇 |
药学 | 66篇 |
中国医学 | 1篇 |
肿瘤学 | 104篇 |
出版年
2023年 | 3篇 |
2022年 | 10篇 |
2021年 | 21篇 |
2020年 | 13篇 |
2019年 | 26篇 |
2018年 | 32篇 |
2017年 | 15篇 |
2016年 | 26篇 |
2015年 | 43篇 |
2014年 | 63篇 |
2013年 | 78篇 |
2012年 | 89篇 |
2011年 | 115篇 |
2010年 | 59篇 |
2009年 | 64篇 |
2008年 | 78篇 |
2007年 | 75篇 |
2006年 | 92篇 |
2005年 | 89篇 |
2004年 | 78篇 |
2003年 | 82篇 |
2002年 | 65篇 |
2001年 | 28篇 |
2000年 | 44篇 |
1999年 | 22篇 |
1998年 | 16篇 |
1997年 | 7篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 10篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 10篇 |
1987年 | 17篇 |
1986年 | 12篇 |
1985年 | 6篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 12篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1976年 | 8篇 |
1974年 | 3篇 |
1927年 | 5篇 |
1926年 | 5篇 |
1924年 | 6篇 |
1921年 | 2篇 |
排序方式: 共有1577条查询结果,搜索用时 15 毫秒
31.
32.
33.
Tara M. Weitz David Gate Kavon Rezai-Zadeh Terrence Town 《The American journal of pathology》2014,184(11):2855-2861
Activated microglia are associated with amyloid plaques in transgenic mouse models of cerebral amyloidosis and in human Alzheimer disease; yet, their implication in Alzheimer disease pathogenesis remains unclear. It has been suggested that microglia play dual roles depending on the context of activation, contributing negatively to disease pathogenesis by secreting proinflammatory innate cytokines or performing a beneficial role via phagocytosis of amyloid beta (Aβ) deposits. Toll-like receptors, most of which signal through the adaptor protein myeloid differentiation factor 88 (MyD88), have been suggested as candidate Aβ innate pattern recognition receptors. It was recently reported that MyD88 deficiency reduced brain amyloid pathology and microglial activation. To assess a putative role of MyD88 in cerebral amyloidosis and glial activation in APPswe/PS1ΔE9 (APP/PS1) mice, we crossed MyD88-deficient (MyD88−/−) mice with APP/PS1 mice, interbred first filial offspring, and studied APP/PS1 MyD88+/+, APP/PS1 MyD88+/−, and APP/PS1 MyD88−/− cohorts. Biochemical analysis of detergent-soluble and detergent-insoluble Aβ1-40 or Aβ1-42 in brain homogenates did not reveal significant between-group differences. Furthermore, no significant differences were observed on amyloid plaque load or soluble fibrillar Aβ by quantitative immunohistochemical analysis. In addition, neither activated microglia nor astrocytes differed among the three groups. These data suggest that MyD88 signaling is dispensable for Aβ-induced glial activation and does not significantly affect the nature or extent of cerebral β-amyloidosis in APP/PS1 mice.Alzheimer disease (AD) is an insidious public health threat characterized by deposition of β-amyloid as senile plaques, formation of neurofibrillary tangles, and large-scale cortical neuronal loss leading to dementia. In addition to these pathognomonic features of the disease, AD patients exhibit low-level chronic neuroinflammation. This is hallmarked by the spatial and temporal occurrence of activated microglia with amyloid beta (Aβ) deposits. Yet, the mechanisms by which microglia recognize and respond to Aβ accumulation remain unclear. Current evidence suggests that there are varied forms of activated microglia in AD, some of which are detrimental and others beneficial.1 Because microglial activation is a complex continuum of varied responses,2 it stands to reason that a wide array of immune molecules may orchestrate microglial responses to Aβ. Ultimately, a clearer understanding of the pathways leading to beneficial microglial responses and clearance of misfolded proteins could open new avenues for AD treatment.Numerous recent studies have proposed that Toll-like receptors (TLRs) play a role in the microglial response to Aβ and, more specifically, that aggregated Aβ can activate microglia via TLRs.3–11 Most TLRs (except TLR3) signal through the adaptor protein myeloid differentiation factor 88 (MyD88), suggesting that it may play an important role in microglial activation in response to cerebral amyloid accumulation. To test this possibility, two recent studies crossed MyD88 knockout mice with APP/PS1 mouse models of cerebral amyloid deposition and examined effects on cognitive deficits and AD-like pathology. In one study, it was reported that MyD88 deficiency of the doubly transgenic APPswe/PS1dE9 mouse reduced cerebral amyloid pathology and microglial activation and decreased expression of CX3CR1 in 10-month-old animals.12 Lim and coworkers12 suggested that inhibiting MyD88-associated TLR signaling would alter the microglial activation state, and they reported less cerebral amyloid deposition in this cross. However, their findings were perplexing given previous reports showing that activation of TLRs leads to decreased amyloid load and increased Aβ phagocytosis, leading to the hypothesis that MyD88 deficiency would either cause buildup of amyloid or have no effect on amyloid levels in APP/PS1 mice.4,6,11,13–15 Another recent study published findings more consistent with this hypothesis, demonstrating that APPswe/PS1A246E mice heterozygous for MyD88 had accelerated spatial learning and memory deficits and increased levels of soluble Aβ oligomers. These results led the authors to conclude that MyD88-mediated activation of microglia was protective in the context of cerebral amyloid deposition.16 In an attempt to clarify the uncertainty surrounding this critical question, we crossed APPswe/PS1dE9 (APP/PS1) mice with MyD88 knockout (MyD88−/−) mice (both on a C57BL/6 background) and analyzed APP/PS1 MyD88+/+, APP/PS1 MyD88+/−, and APP/PS1 MyD88−/− cohorts for Alzheimer-like pathology at 15 months of age. 相似文献
34.
Kraft DJ Ni R Smallenburg F Hermes M Yoon K Weitz DA van Blaaderen A Groenewold J Dijkstra M Kegel WK 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(27):10787-10792
Colloidal particles with site-specific directional interactions, so called "patchy particles", are promising candidates for bottom-up assembly routes towards complex structures with rationally designed properties. Here we present an experimental realization of patchy colloidal particles based on material independent depletion interaction and surface roughness. Curved, smooth patches on rough colloids are shown to be exclusively attractive due to their different overlap volumes. We discuss in detail the case of colloids with one patch that serves as a model for molecular surfactants both with respect to their geometry and their interactions. These one-patch particles assemble into clusters that resemble surfactant micelles with the smooth and attractive sides of the colloids located at the interior. We term these clusters "colloidal micelles". Direct Monte Carlo simulations starting from a homogeneous state give rise to cluster size distributions that are in good agreement with those found in experiments. Important differences with surfactant micelles originate from the colloidal character of our model system and are investigated by simulations and addressed theoretically. Our new "patchy" model system opens up the possibility for self-assembly studies into finite-sized superstructures as well as crystals with as of yet inaccessible structures. 相似文献
35.
36.
Nuh N. Rahbari MD Heike Elbers MD Vasileios Askoxylakis MD Edith Motschall Ulrich Bork MD Markus W. Büchler MD Jürgen Weitz MD Moritz Koch MD 《Annals of surgical oncology》2013,20(13):4169-4182
Background
Although neoadjuvant radiotherapy may improve local control of rectal cancer, its clinical value requires further evaluation as a result of potential side effects and advances in surgical technique. A meta-analysis was performed to assess effectiveness and safety of neoadjuvant radiotherapy in the management of rectal cancer.Methods
The following databases were searched: the Cochrane Library, Biosis, Web of Science, Embase, ASCO Abstracts and WHO International Clinical Trials Registry Platform. Randomized controlled trials on the following comparisons were included: (1) neoadjuvant therapy versus surgery alone and (2) neoadjuvant chemoradiotherapy versus neoadjuvant radiotherapy.Results
We identified 17 and 5 relevant trials that enrolled 8,568 and 2,393 patients, respectively. Neoadjuvant radiotherapy improved local control (hazard ratio 0.59; 95 % confidence interval 0.48–0.72) compared to surgery alone even after total mesorectal excision, whereas its benefit in overall survival just failed to reach statistical significance (0.93; 0.85–1.00). However, it was associated with increased perioperative mortality (1.48; 1.08–2.03), in particular if a dose of 5 Gy per fraction was administered (1.85; 1.23–2.78). Chemoradiotherapy improved local control as opposed to radiotherapy (0.53; 0.39–0.72), with no impact on perioperative outcome and long-term survival.Conclusions
Neoadjuvant radiotherapy improves local control in patients with rectal cancer, particularly when chemoradiotherapy is administered. The question if the use of more effective chemotherapy protocols improves overall survival warrants further investigation. 相似文献37.
Jingjing Qian Linda Simoni-Wastila Gail B. Rattinger Susan Lehmann Patricia Langenberg Ilene H. Zuckerman Michael Terrin 《General hospital psychiatry》2013
Objective
Depression is prevalent in chronic obstructive pulmonary disease (COPD) patients and a risk factor for COPD exacerbation and death. The objective of this study was to determine the associations of depression diagnosis and antidepressant treatment with mortality among Social Security Disability Insurance (SSDI)-eligible (age < 65 years who had permanent physical or mental disabilities) Medicare beneficiaries with COPD.Method
This retrospective cohort study used a 5% random sample of SSDI-eligible Medicare beneficiaries with COPD in stand-alone Part D plans during 2006–2008 (n= 17,320). COPD and depression diagnoses were assessed during 2006. Evidence of antidepressant treatment was measured in 2006–2008. All-cause mortality was measured in 2007–2008. Cox proportional hazards models were used to examine the associations of depression diagnosis with mortality and, among depressed beneficiaries, antidepressant treatment (time dependent) with mortality after controlling for covariates.Results
More than one third (37.3%) of SSDI-eligible beneficiaries with COPD had a baseline depression diagnosis; of those, 86.8% had evidence of antidepressant treatment. Baseline depression diagnosis was an independent risk factor for 2-year mortality [hazard ratio (HR)=1.21; 99% confidence interval (CI)=1.07–1.37]. Among depressed beneficiaries, receiving antidepressant treatment was associated with significantly lower mortality (HR=0.55; 99% CI=0.44–0.68).Conclusion
Proactive antidepressant treatment should be considered as an intervention to reduce mortality for this young and disabled Medicare population. 相似文献38.
Kent J. Kilbourn Stephanie Levy Ilene Staff Inam Kureshi Louise McCullough 《Clinical neurology and neurosurgery》2013
Background
Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated.Methods
A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n = 299) was conducted. Those patients who underwent an echocardiogram were identified (n = 120) and were assigned to the NCM (n = 49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia.Results
16% of aSAH patients developed NCM. Mortality was higher (p < .001) in the NCM group (n = 23[46.9%]) than in the non-CM group (n = 28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p = .002) and 12 months (p = .014). The Hunt–Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p = .002) as well as at 1 year (p = .014). NCM was associated with both death (p = .047 CI, 1.012–7.288) and vasospasm (p = .008 CI, 1.34–6.66) after correction for Hunt–Hess grade. Tobacco use (p < .001) and a history of diabetes mellitus (p < .009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p = .047) in multivariate analysis.Conclusion
NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality. 相似文献39.