全文获取类型
收费全文 | 464篇 |
免费 | 30篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 10篇 |
妇产科学 | 18篇 |
基础医学 | 65篇 |
口腔科学 | 13篇 |
临床医学 | 36篇 |
内科学 | 135篇 |
皮肤病学 | 4篇 |
神经病学 | 40篇 |
特种医学 | 10篇 |
外科学 | 35篇 |
综合类 | 3篇 |
预防医学 | 44篇 |
眼科学 | 1篇 |
药学 | 33篇 |
肿瘤学 | 53篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 16篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 21篇 |
2013年 | 26篇 |
2012年 | 46篇 |
2011年 | 32篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 29篇 |
2007年 | 25篇 |
2006年 | 31篇 |
2005年 | 36篇 |
2004年 | 28篇 |
2003年 | 27篇 |
2002年 | 29篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
排序方式: 共有502条查询结果,搜索用时 312 毫秒
1.
Danila Valmori Jackeline F. Romero Ying Men Janet L. Maryanski Pedro Romero Giampietro Corradin 《European journal of immunology》1994,24(6):1458-1462
We have previously demonstrated that it is possible to induce a consistent and strong cytolytic T lymphocyte (CTL) response to synthetic peptides, corresponding to poorly immunogenic malaria CTL epitopes, by co-injecting them with peptides representing defined T helper (Th) epitopes in incomplete Freund's adjuvant (IFA). In this study we have tested different immunization protocols to improve further the elicitation of the CTL response. We show that the CTL response to a mixture of Th + CTL peptides administered in IFA was further enhanced by a previous injection of the Th epitope peptide in IFA. Moreover, we found that the response could be significantly augmented by a pre-injection of IFA alone. This enhancement was observed only if the Th epitope was also present in the second injection. The number of lymph node cells recovered was 2–3-fold higher in mice pre-injected with IFA, but the increase in specific CTL activity, expressed as lytic units per animal, by pre-injection of IFA was at least 10–20-fold. Thus, pre-injection of IFA clearly increases the magnitude of a subsequent CTL response. 相似文献
2.
3.
4.
Fernanda Neves de Carvalho Carolina Toniolo Zenatti Danila Cassia Reis Santana Juliana Maria da Silva Juliane Cristina Oliveira dos As Katia Kisielow dos Anjos Jessica Sigari Cassia de Lima Santos Marcelle Guerra Olivia Pereira Barros Tomaz Cochemore Roberto Camargo Narciso Mario Lucio Baptista Filho 《The Brazilian journal of infectious diseases》2018
5.
James L. Hadler Richard N. Danila Paul R. Cieslak James I. Meek William Schaffner Kirk E. Smith Matthew L. Cartter Lee H. Harrison Duc J. Vugia Ruth Lynfield 《Emerging infectious diseases》2015,21(9):1510-1515
The Emerging Infections Program (EIP) is a collaboration between the Centers for Disease Control and Prevention and 10 state health departments working with academic partners to conduct active population-based surveillance and special studies for several emerging infectious disease issues determined to need special attention. The Centers for Disease Control and Prevention funds the 10 EIP sites through cooperative agreements. Our objective was to highlight 1) what being an EIP site has meant for participating health departments and associated academic centers, including accomplishments and challenges, and 2) the synergy between the state and federal levels that has resulted from the collaborative relationship. Sharing these experiences should provide constructive insight to other public health programs and other countries contemplating a collaborative federal–local approach to collective public health challenges. 相似文献
6.
Silvia Angela Debonis Alberto Bongiovanni Federica Pieri Valentina Fausti Alessandro De Vita Nada Riva Lorena Gurrieri Silvia Vanni Danila Diano Laura Mercatali Toni Ibrahim 《Medicine》2021,100(20)
Rationale:Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach. However, the genetic landscape of this tumor is still not fully understood and treatment options are limited, especially in the majority of ALK-negative tumors.Patient concerns:We describe the clinical case of a healthy 18-year-old female in whom a pulmonary nodule was incidentally detectedDiagnoses:Following a small increase in the size of the nodule, the patient underwent both 18FDG-PET/CT and 68Ga-PET/CT, resulting in a suspicion of bronchial hamartoma.Interventions:The patient underwent surgery and a salivary gland-like lung tumor was diagnosed.Outcomes:After surgery, the patient was referred to our cancer center, where a review of the histology slides gave a final diagnosis of ALK-negative lung IMT. Given the histology, it was decided not to administer adjuvant therapy and the patient was placed in a 3-monthly follow-up program. The patient is still disease-free 2 years post-surgery.Lessons:Although there is no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. Our review of the literature on IMT and other kinase fusions revealed, in addition to ALK rearrangements, the potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor. 相似文献
7.
Sujata Tewari Marcel Diano Rimal Bera Quoc Nguyen Hemalatha Parekh 《Alcoholism, clinical and experimental research》1992,16(3):436-442
The long-term effects of prenatal ethanol exposure on the properties of brain polysomes and the proliferative responses of lymphocytes to mitogenic stimulation in adult offspring were assessed. Female Sprague-Dawley rats either ingested the control or 6.6% ethanol-containing Lieber-DeCarli liquid diet during the 3rd trimester of pregnancy. Controls were age-matched and pair-fed. At 42 to 72 days of age, ethanol effects were evaluated on the (1) polysomal properties in the cerebral hemispheres, cerebellum, and hippocampal regions of the brain after translation in a messenger RNA (mRNA)-dependent rabbit reticulocyte lysate system and (2) immunologic functions of lymphocytes cultured from spleen cells by measuring their responses to mitogenic stimulation. Results showed long-term adverse effects of in utero ethanol exposure on the polysomal RNA translation in each of the three brain regions tested with free polysomal mRNAs affected more than the bound polysomal mRNAs. Of these, the hippocampal region appeared to sustain the most injurious effects. In addition, a suppression of the mitogen-induced lymphocyte proliferative responses were present under these conditions. The degree of suppression varied with the specific mitogen used. Data suggest that the ethanol effects on the CNS and lymphocyte proliferation are most possibly irreversible, and in the case of the CNS, a post-translational modification by ethanol is indicated. The reduced lymphocyte responses are suggestive of a possible interference by ethanol of the synthesis of interleukin-2 (IL-2) and/or a reduced binding of IL-2 with its receptor (IL-2 receptors). 相似文献
8.
Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice
Jung Dae Kim Chitoku Toda Giuseppe D’Agostino Caroline J. Zeiss Ralph J. DiLeone John D. Elsworth Richard G. Kibbey Owen Chan Brandon K. Harvey Christopher T. Richie Mari Savolainen Timo My?h?nen Jin Kwon Jeong Sabrina Diano 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(32):11876-11881
Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prepgt/gt) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, , impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prepgt/gt and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prepgt/gt and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prepgt/gt mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus–PREP reversed the glucose-intolerant phenotype of the Prepgt/gt mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.Prolyl endopeptidase (PREP; EC 3.4.21.26) is a highly conserved enzyme ( S170921). In humans and rodents it is highly expressed in the brain (2), including the cortex, striatum, hypothalamus, hippocampus, and amygdala (3–6). The physiological role of PREP remains elusive (7). Many studies have focused on the putative effect of PREP on neuropeptide levels because this enzyme could function to cleave virtually all neuropeptides shorter than 30 amino acids that contain an internal proline residue (8).However, much of our understanding of this enzyme is based on in vitro data. Because PREP’s putative targets regulate a large number of signaling pathways, PREP has the capacity to regulate a variety of cellular tasks.To gain a better understanding of the role of PREP in the hypothalamus, we analyzed the effect of PREP knockdown on hypothalamic mechanisms including glucose and energy metabolism. 相似文献
9.
10.
WH Brown MP Gillum HY Lee JP Camporez XM Zhang JK Jeong TC Alves DM Erion BA Guigni M Kahn VT Samuel BF Cravatt S Diano GI Shulman 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(37):14966-14971
Fatty acid amide hydrolase (FAAH) knockout mice are prone to excess energy storage and adiposity, whereas mutations in FAAH are associated with obesity in humans. However, the molecular mechanism by which FAAH affects energy expenditure (EE) remains unknown. Here we show that reduced energy expenditure in FAAH(-/-) mice could be attributed to decreased circulating triiodothyronine and thyroxine concentrations secondary to reduced mRNA expression of both pituitary thyroid-stimulating hormone and hypothalamic thyrotropin-releasing hormone. These reductions in the hypothalamic-pituitary-thyroid axis were associated with activation of hypothalamic peroxisome proliferating-activated receptor γ (PPARγ), and increased hypothalamic deiodinase 2 expression. Infusion of NAEs (anandamide and palmitoylethanolamide) recapitulated increases in PPARγ-mediated decreases in EE. FAAH(-/-) mice were also prone to diet-induced hepatic insulin resistance, which could be attributed to increased hepatic diacylglycerol content and protein kinase Cε activation. Our data indicate that FAAH deletion, and the resulting increases in NAEs, predispose mice to ectopic lipid storage and hepatic insulin resistance by promoting centrally mediated hypothyroidism. 相似文献