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排序方式: 共有347条查询结果,搜索用时 13 毫秒
91.
Mohamed Labib Salem William E Gillanders Andre N Kadima Sabry El-Naggar Mark P Rubinstein Marina Demcheva John N Vournakis David J Cole 《Journal of interferon & cytokine research》2006,26(9):593-608
It has become increasingly apparent that the ability to generate an optimal host immune response requires effective cross talk between the innate and adaptive components of the immune system. Pro-inflammatory cytokines, in particular those that can induce a danger signal, often called signal 3, are crucial in this role of initiating and augmenting the presentation of exogenous antigen to T cells by dendritic cells. Interleukin-12 (IL-12) in particular has been defined as a "signal 3" cytokine required for the antigen cross priming. Given this unique interactive function, a significant amount of work has been performed to define possible therapeutic applications for IL-12. Systemic IL-12 administration can clearly act as a potent adjuvant for postvaccination T cell responses in a variety of diseases. As an example, in the cancer setting, systemic IL-12 is capable of suppressing tumor growth, metastasis, and angiogenesis in vivo. IL-12, however, has been associated with significant dose- and schedule-dependent toxicity in early clinical trials, results that have proven to be a major obstacle to its clinical application. Recent research has focused on decreasing the toxicity of IL-12 using different delivery approaches, including virus-based and gene-modified cell-based delivery. Although effective, these approaches also have limitations, including the generation of neutralizing antibodies, in addition to lacking the simplicity and versatility required for universal clinical application. Thus, there is a significant interest in the development of alternative delivery approaches for IL-12 administration that can overcome these issues. Several nonviral delivery approaches for IL-12 protein or gene expression vectors are being defined, including alum, liposomes, and polymer-based delivery. These developing approaches have shown promising adjuvant effects with significantly lessened systemic toxicity. This article discusses the potential capabilities of these nonvirus-based IL-12 delivery systems in different disease settings, including allergy, infection, and cancer. 相似文献
92.
Lee LYK, Lee DTF, Woo J. The psychosocial effect of tai chi on nursing home residents. J Clin Nurs 2010; 19: 927–38. 相似文献
93.
Chen Y Zheng B Robbins DH Lewin DN Mikhitarian K Graham A Rumpp L Glenn T Gillanders WE Cole DJ Lu X Hoffman BJ Mitas M 《International journal of cancer. Journal international du cancer》2007,120(7):1511-1517
To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined," the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29), 92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in 3 samples for which the initial cytological diagnosis was "suspicious" and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis. 相似文献
94.
Fields RC Aft RL Gillanders WE Eberlein TJ Margenthaler JA 《American journal of surgery》2008,196(4):559-561
Background
Surgery is the main treatment for primary breast sarcoma (PBS). Here we characterize this disease and determine factors associated with use of adjuvant therapy.Methods
Records of patients with PBS from 1986 to 2006 were reviewed. Overall survival (OS) was estimated by Kaplan-Meier. Relationships between patient variables and OS were determined using univariate Cox proportional hazard models.Results
Thirteen patients with PBS were identified; 10 patients underwent mastectomy, and 3 underwent partial mastectomy. Six patients underwent axillary staging; none were positive. Patients with tumors >5 cm were more likely to undergo radiation therapy (P <.05). Local recurrence occurred in 7 patients. Metastatic disease was present in 2 patients at diagnosis, and 6 patients developed metastatic disease; all 8 patients died from their disease. Five patients remained disease free. Five-year OS was 67% (83% for tumors <5 cm and 42% for tumors >5 cm). Tumor size was significantly associated with OS (relative risk = 1.1/1 cm increase in size > 5 cm).Conclusions
Treatment for PBS is excision to clear margins. Axillary staging is not indicated. Tumor size >5 cm is the only significant prognostic indicator of overall survival. 相似文献95.
Feiya Ou Stephen T. Ferris Sunkyung Kim Renee Wu David A. Anderson III Tian-Tian Liu Suin Jo Michael Y. Chen William E. Gillanders Theresa L. Murphy Kenneth M. Murphy 《European journal of immunology》2023,53(9):2250201
In vitro culture of bone marrow (BM) with Fms-like tyrosine kinase 3 ligand (Flt3L) is widely used to study development and function of type 1 conventional dendritic cells (cDC1). Hematopoietic stem cells (HSCs) and many progenitor populations that possess cDC1 potential in vivo do not express Flt3 and thus may not contribute to Flt3L-mediated cDC1 production in vitro. Here, we present a KitL/Flt3L protocol that recruits such HSCs and progenitors into the production of cDC1. Kit ligand (KitL) is used to expand HSCs and early progenitors lacking Flt3 expression into later stage where Flt3 is expressed. Following this initial KitL phase, a second Flt3L phase is used to support the final production of DCs. With this two-stage culture, we achieved approximately tenfold increased production of both cDC1 and cDC2 compared to Flt3L culture. cDC1 derived from this culture are similar to in vivo cDC1 in their dependence on IRF8, ability to produce IL-12, and induction of tumor regression in cDC1-deficient tumor-bearing mice. This KitL/Flt3L system for cDC1 production will be useful in further analysis of cDC1 that rely on in vitro generation from BM. 相似文献
96.
Hilary Faust LK Metthew Lam Meghan J. Hotz Danielle Qing Nilam S. Mangalmurti 《Vox sanguinis》2020,115(8):729-734
RBC transfusion is associated with increased morbidity and mortality in critically ill patients. Endothelial cell necroptosis and subsequent damage-associated molecular pattern (DAMP) release has been identified as a mechanism of injury following RBC transfusion. Mounting evidence implicates the pro-inflammatory pattern recognition receptor, Receptor for Advanced Glycation End Products (RAGE), in initiating cell death programmes such as necroptosis. Here, we demonstrate the role of RAGE in endothelial necroptosis, as deletion of RAGE attenuates necroptotic cell death in response to TNFα, LPS or CpG-DNA. We show direct interaction of RAGE with the critical mediator of necroptosis, Receptor Interacting Protein Kinase 3 (RIPK3), during necroptosis. Furthermore, we observe decreased plasma High Mobility Group Box 1 (HMGB1) and RIPK3 levels in RAGE deficient mice compared to WT mice post-transfusion, substantiating the role for RAGE in transfusion-induced DAMP release in vivo. Collectively, these findings underscore RAGE as an essential mediator of regulated necrosis and post-transfusion DAMP release. Further studies to understand the role of RAGE and the necroptotic pathway in transfusion-induced organ injury may offer key targets to mitigate transfusion-related risks, including the risk of ARDS, in susceptible hosts. 相似文献
97.
98.
99.
S. Muenst A. R. Schaerli F. Gao S. Däster E. Trella R. A. Droeser M. G. Muraro P. Zajac R. Zanetti W. E. Gillanders W. P. Weber S. D. Soysal 《Breast cancer research and treatment》2014,146(1):15-24
Recent studies in multiple epithelial cancers have shown that the inhibitory receptor programmed cell death 1 (PD-1) is expressed on tumor-infiltrating lymphocytes and/or programmed death ligand 1 (PD-L1) is expressed on tumor cells, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway. In addition, phase 1 clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 have shown promising results in several human cancers. The purpose of this study was to investigate the impact of PD-L1 expression in human breast cancer specimens. We conducted an immunohistochemistry study using a tissue microarray encompassing 650 evaluable formalin-fixed breast cancer cases with detailed clinical annotation and outcomes data. PD-L1 was expressed in 152 (23.4 %) of the 650 breast cancer specimens. Expression was significantly associated with age, tumor size, AJCC primary tumor classification, tumor grade, lymph node status, absence of ER expression, and high Ki-67 expression. In univariate analysis, PD-L1 expression was associated with a significantly worse OS. In multivariate analysis, PD-L1 expression remained an independent negative prognostic factor for OS. In subset analyses, expression of PD-L1 was associated with significantly worse OS in the luminal B HER2? subtype, the luminal B HER2+ subtype, the HER2 subtype, and the basal-like subtype. This is the first study to demonstrate that PD-L1 expression is an independent negative prognostic factor in human breast cancer. This finding has important implications for the application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease. 相似文献
100.
Mario Schootman PhD Donna B. Jeffe PhD William E. Gillanders MD Rebecca Aft MD PhD 《Cancer》2009,115(4):731-740