全文获取类型
收费全文 | 602篇 |
免费 | 23篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 10篇 |
妇产科学 | 15篇 |
基础医学 | 71篇 |
口腔科学 | 3篇 |
临床医学 | 27篇 |
内科学 | 155篇 |
皮肤病学 | 30篇 |
神经病学 | 42篇 |
特种医学 | 8篇 |
外科学 | 25篇 |
综合类 | 1篇 |
预防医学 | 34篇 |
眼科学 | 25篇 |
药学 | 44篇 |
肿瘤学 | 131篇 |
出版年
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 32篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 13篇 |
2016年 | 7篇 |
2015年 | 22篇 |
2014年 | 23篇 |
2013年 | 21篇 |
2012年 | 61篇 |
2011年 | 48篇 |
2010年 | 27篇 |
2009年 | 26篇 |
2008年 | 43篇 |
2007年 | 56篇 |
2006年 | 48篇 |
2005年 | 33篇 |
2004年 | 39篇 |
2003年 | 23篇 |
2002年 | 17篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1992年 | 10篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有627条查询结果,搜索用时 15 毫秒
41.
Cezary Wójcik Sergio Fazio Adam D. McIntyre Robert A. Hegele 《Journal of clinical lipidology》2018,12(5):1146-1150
We describe a case of a 36-year-old woman with severe hypertriglyceridemia likely caused by double heterozygosity of a known pathogenic APOA5 nonsense variant (p.Q275X) and a novel CREB3L3 nonsense variant (p.C296X) on a background of very strong polygenic susceptibility. Her clinical course worsened with development of eruptive xanthomata after oral administration of 2 mg estradiol twice daily for 2 weeks as part of a medical protocol for intrauterine embryo transfer following in vitro fertilization. Her triglyceride levels decreased to baseline and xanthomata resolved without treatment after discontinuation of hormonal therapy, which also resulted in termination of pregnancy. Before undergoing a second embryo transfer using her natural cycle and no exogenous hormones, the patient started combination therapy with eicosapentaenoic acid ethyl ester and gemfibrozil, leading to an ~80% decrease in triglyceride levels. She continued treatment throughout pregnancy, which progressed to term with the delivery of healthy twins. 相似文献
42.
Shimon Lecht Hadar Arien-Zakay Cezary Marcinkiewicz Peter I. Lelkes Philip Lazarovici 《Journal of molecular neuroscience : MN》2010,41(1):183-192
Nerve growth factor (NGF) was recently characterized as an angiogenic factor inducing proliferation, migration, and capillary
sprouting in endothelial cells (ECs) of different vascular beds. While NGF neuroprotective effects on neurons were described,
its survival-inducing effects on brain capillary ECs were not yet addressed. Using a model of oxygen–glucose deprivation (OGD)
followed by reoxygenation, we demonstrated that NGF conferred protection in brain capillary ECs. These cells express TrkA
and p75NTR receptors and respond to NGF by stimulation of Erk1/2 phosphorylation and stimulation of proliferation and migration. The
NGF protective effect was dose-dependent, inhibited by NGF/TrkA antagonist, K252a, and required presence of NGF during both
OGD and reoxygenation phases while the major protective effect was related to decreased cell death during the reoxygenation
phase. A causal relationship was found between NGF-induced protection and attenuation of OGD-induced Erk1/2 phosphorylation,
supporting the death-promoting role of insult-induced Erk1/2 phosphorylation in the brain capillary ECs. These results emphasize
the importance of NGF in the process of EC survival in response to ischemic injury and suggest fine-tuning regulation of Erk1/2
phosphorylation, extending the neuroprotective impact of NGF from sympathetic neuroendocrine cells to brain capillary ECs
as the other element in the neurovascular tandem. 相似文献
43.
MEG and EEG studies of event-related responses often involve comparisons of grand averages, requiring homogeneity of the variances. Here, we examine the possibility, implied by the nature of neural sources and the measuring principles involved, that the M100 component of auditory-evoked magnetic fields of different subjects, hemispheres, to different stimuli, and at different sensors differs by scaling factors. Such a multiplicative model predicts a linear increase in the standard deviation with the mean, and thus would have important implications for averaging and comparing such data. Our analyses, at the sensor and the source level, clearly show that the multiplicative model applies. We therefore propose geometric, rather than arithmetic, averaging of the M100 component across subjects and suggest a novel and superior normalization procedure. Our results question the justification of the common practice of subtracting arithmetic grand averages. 相似文献
44.
45.
The contribution of inflammatory process to the modulation of platelet response to acetylsalicylic acid (ASA) remains obscure. In our study, we examined the in vitro effect of C-reactive protein (CRP) on the ASA-mediated inhibition of collagen-stimulated platelet reactivity. Influence of CRP on platelet responsiveness to ASA was analysed using classical turbidimetric aggregation and flow cytometry. When acting alone, both C-reactive protein and ASA inhibited collagen-dependent platelet aggregation and reduced the expressions of two platelet surface membrane activation markers: P-selectin and activated GPIIbIIIa complex. Compared to the effects observed for ASA alone, the simultaneous action of both agents lead to further reductions in platelet aggregation (by 56.7+/-1.0% vs. 14.9+/-0.6%, p<0.0001) and lowered the expressions of platelet surface membrane P-selectin (by 72.1+/-5.3% vs. 65.0+/-6.0%, p<0.01) and activated GPIIbIIIa (by 67.0+/-5.6% vs. 47.7+/-8.3%, p<0.01). In general, our findings showed for the first time the augmenting effect of native C-reactive protein in the antiplatelet action of acetylsalicylic acid. Thus, we conclude that the effectiveness of aspirin therapy may strongly depend upon the presence of native CRP in circulation. 相似文献
46.
Wang JY Gualco E Peruzzi F Sawaya BE Passiatore G Marcinkiewicz C Staniszewska I Ferrante P Amini S Khalili K Reiss K 《Journal of neuroscience research》2007,85(11):2360-2373
Tumor necrosis factor-alpha (TNFalpha) released in the brain by HIV-activated macrophages/microglia is suspected to compromise neuronal survival. Previously, we have demonstrated that activated receptor for insulin-like growth factor I (IGF-IR) protects neurons from TNFalpha-induced neuronal damage (Wang et al. [ 2006] J. Neurosci. Res. 83:7-18). Because TNFalpha triggers phosphorylation of insulin receptor substrate 1 (IRS-1) on serine residues (pS-IRS-1; Rui et al. [ 2001] J. Clin. Invest. 107:181-189), and pS-IRS-1 binds integrins (Reiss et al. [ 2001] Oncogene 20:490-500), we asked how these events affect neuronal processes. We show that beta1-integrin and pS-IRS-1 colocalize in PC12 cells and in primary cortical neurons. TNFalpha treatment elevated membrane-associated pS-IRS-1, enhanced pS-IRS-1 interaction with beta1-integrin, and attenuated cell attachment to collagen IV. In contrast, IGF-I inhibited pS-IRS-1-beta1-integrin complexes and improved cell attachment. The domain of IRS-1 involved in beta1-integrin binding mapped between amino acids 426 and 740, and the expression of 426-740/IRS-1 mutant attenuated neuronal outgrowth. Our results indicate that TNFalpha facilitates the interaction of pS-IRS-1 and beta1-integrin and destabilizes neuronal processes. IGF-I counteracts TNFalpha-mediated accumulation of pS-IRS-1-beta1-integrin complexes supporting the stability of neuronal processes. 相似文献
47.
48.
Wcislo G Szarlej-Wcislo K Szczylik C 《Journal of cancer research and clinical oncology》2007,133(8):533-538
Objective There has been only one report available that focuses on the treatment with imatinib mesylate of two individual persons with
aggressive fibromatosis. The authors concluded that after long-term treatment, for 9 and 11 months, with imatinib mesylate,
both patients demonstrated radiographic and clinical responses. The novel therapy should be considered as salvage in patients
with aggressive fibromatosis expressed platelet-derived growth factor receptor—alfa, beta (PDGFR-alfa, PDGFR-beta), and/or
c-kit, whose tumors are uncontrollable by the standard management. On the other hand, the number of kinases blocked by imatinib
mesylate is notching up, for instance the tyrosine kinase, which is associated with macrophage-colony stimulating factor receptor
(M-CSFR).
Methods The patient was suffering from aggressive fibromatosis after prior therapy including surgery (R2), radiotherapy, and systemic
treatment with combination of tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c-kit (CD117),
and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and beta were not assessed. The tests for both assessed molecules
revealed negative results. In spite of this, the patient underwent a unique treatment with imatinib mesylate at the dose of
400 mg orally once daily for 3 years and 2 months.
Results After three months of the therapy, radiographic (met criteria of SD but small decrease of the tumor was noted) and clinical
responses were recorded for the first time. The same was seen after 6 and 13 months of therapy continuation with imatinib
mesylate. Currently, the patient is treated with imatinib mesylate (400 mg orally once daily) without any toxicity effects.
The last MRI revealed readily a smaller tumor (35 × 20 mm) after such a therapy lasted more than 3 years.
Conclusions Treatment with imatinib mesyalte has been a well-accepted therapy for chronic myelagenous leukemia (CML) and gastrointestinal
stromal tumors (GIST). There have been established four kinases (p210bcr/abl, c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other potential targets will be discovered
as it has lately been determined that M-CSFR kinase activity was blocked by imatinib mesylate. The salvage therapy for aggressive
fibromatosis with imatinib mesylate seems to be an attractive opportunity for patients with the advanced disease, whose prior
therapy failed. 相似文献
49.
50.
Maruszak A Canter JA Styczyńska M Zekanowski C Barcikowska M 《Neurobiology of aging》2009,30(11):1749-1755
We evaluated the involvement of the major Caucasian-specific mitochondrial haplogroups (H, I, J, K, T, U, V, W and X), haplogroup clusters (HV, UK, TJ, IWX) and two functional mtSNPs (4216, 4917) in the pathogenesis of Alzheimer's disease (AD) in the Polish population. The frequency distribution of mtDNA haplogroups was non-randomly associated with APOE4 status (chi(2)=73.17, df=1, p<0.0001, OR=5.97, 95% CI 3.90-9.12), however, no haplogroup-specific neutralizing of the APOE4 allele influence was detected. Multivariate analysis suggested the opposite-APOE4 status could modulate the effect of mtDNA haplogroups. We found that HV cluster is significantly associated with the risk of AD, regardless of the APOE4 status (OR=1.59, 95% CI, 1.04-2.44, p=0.032). Contrary to the previous studies, we report no evidence for the involvement of haplogroup U, K, J or T in AD risk. We conclude that further analysis of subtypes of haplogroup H would be necessary to decipher the relation of HV cluster with AD. 相似文献