全文获取类型
收费全文 | 1127篇 |
免费 | 78篇 |
国内免费 | 14篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 36篇 |
妇产科学 | 14篇 |
基础医学 | 171篇 |
口腔科学 | 12篇 |
临床医学 | 198篇 |
内科学 | 176篇 |
皮肤病学 | 10篇 |
神经病学 | 44篇 |
特种医学 | 91篇 |
外科学 | 171篇 |
综合类 | 52篇 |
预防医学 | 79篇 |
眼科学 | 26篇 |
药学 | 50篇 |
肿瘤学 | 86篇 |
出版年
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 18篇 |
2017年 | 15篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 22篇 |
2013年 | 36篇 |
2012年 | 42篇 |
2011年 | 49篇 |
2010年 | 43篇 |
2009年 | 45篇 |
2008年 | 49篇 |
2007年 | 50篇 |
2006年 | 62篇 |
2005年 | 46篇 |
2004年 | 75篇 |
2003年 | 40篇 |
2002年 | 32篇 |
2001年 | 39篇 |
2000年 | 34篇 |
1999年 | 28篇 |
1998年 | 30篇 |
1997年 | 27篇 |
1996年 | 33篇 |
1995年 | 38篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 22篇 |
1991年 | 21篇 |
1990年 | 14篇 |
1989年 | 31篇 |
1988年 | 27篇 |
1987年 | 22篇 |
1986年 | 23篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 15篇 |
1982年 | 9篇 |
1981年 | 11篇 |
1980年 | 11篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1971年 | 5篇 |
1970年 | 4篇 |
排序方式: 共有1219条查询结果,搜索用时 0 毫秒
991.
992.
Christopher M. Wittich Christopher M. Burkle William L. Lanier 《Mayo Clinic proceedings. Mayo Clinic》2012,87(10):982-990
The term off-label drug use (OLDU) is used extensively in the medical literature, continuing medical education exercises, and the media. Yet, we propose that many health care professionals have an underappreciation of its definition, prevalence, and implications. This article introduces and answers 10 questions regarding OLDU in an effort to clarify the practice's meaning, breadth of application, acceptance, and liabilities. Off-label drug use involves prescribing medications for indications, or using a dosage or dosage form, that have not been approved by the US Food and Drug Administration. Since the Food and Drug Administration does not regulate the practice of medicine, OLDU has become common. It occurs in every specialty of medicine, but it may be more common in areas of medicine in which the patient population is less likely to be included in clinical trials (eg, pediatric, pregnant, or psychiatric patients). Pharmaceutical companies are not allowed to promote their medications for an off-label use, which has lead to several large settlements for illegal marketing. To limit liability, physicians should prescribe medications only for indications that they believe are in the best interest of the patient. In addition, health care professionals should educate themselves about OLDU to weigh the risks and benefits and provide the best possible care for their patients. 相似文献
993.
Safety and tolerability of omalizumab 总被引:1,自引:0,他引:1
J. Corren T. B. Casale B. Lanier R. Buhl S. Holgate P. Jimenez 《Clinical and experimental allergy》2009,39(6):788-797
Background Omalizumab (Xolair® ) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma.
Objective To review clinical study data to assess the safety profile of omalizumab.
Methods We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia.
Results Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003–December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab.
Conclusion Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile. 相似文献
Objective To review clinical study data to assess the safety profile of omalizumab.
Methods We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia.
Results Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003–December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab.
Conclusion Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile. 相似文献
994.
Sato M Cismowski MJ Toyota E Smrcka AV Lucchesi PA Chilian WM Lanier SM 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(3):797-802
As part of a broader effort to identify postreceptor signal regulators involved in specific diseases or organ adaptation, we used an expression cloning system in Saccharomyces cerevisiae to screen cDNA libraries from rat ischemic myocardium, human heart, and a prostate leiomyosarcoma for entities that activated G protein signaling in the absence of a G protein coupled receptor. We report the characterization of activator of G protein signaling (AGS) 8 (KIAA1866), isolated from a rat heart model of repetitive transient ischemia. AGS8 mRNA was induced in response to ventricular ischemia but not by tachycardia, hypertrophy, or failure. Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not in rat aortic smooth muscle cells, endothelial cells, or cardiac fibroblasts, suggesting a myocyte-specific adaptation mechanism involving remodeling of G protein signaling pathways. The bioactivity of AGS8 in the yeast-based assay was independent of guanine nucleotide exchange by Galpha, suggesting an impact on subunit interactions. Subsequent studies indicated that AGS8 interacts directly with Gbetagamma and this occurs in a manner that apparently does not alter the regulation of the effector PLC-beta(2) by Gbetagamma. Mechanistically, AGS8 appears to promote G protein signaling by a previously unrecognized mechanism that involves direct interaction with Gbetagamma. 相似文献
995.
Pulmonary edema after resection of a fourth ventricle tumor: possible evidence for a medulla-mediated mechanism 总被引:1,自引:0,他引:1
A well-recognized fact is that some patients may have development of pulmonary edema in association with disorders of the central nervous system. The origin of this phenomenon, known as neurogenic pulmonary edema, is unclear but may result, in part, from select pulmonary venoconstriction modulated by autonomic outflow from the medulla oblongata. We describe a 21-year-old man who had development of pulmonary edema in association with surgical resection of a brain tumor that was close to the medulla. Other than the possibility of medullary dysfunction, which could have occurred after surgical manipulation, no other risk factor for pulmonary edema was identified. Of note, the patient's blood pressure remained normal throughout the perioperative period, and no fluid overload or primary cardiac dysfunction was evident. This case supports the theory that the medulla is an important anatomic site of origin for neurogenic pulmonary edema and that alterations in medullary function can induce pulmonary edema in humans, independent of systemic hypertension. 相似文献
996.
997.
Several studies suggest a role for the amyloid precursor protein (APP) in neurite outgrowth and synaptogenesis, but the downstream interactions that mediate the function of APP during neuron development are unknown. By introducing interaction-deficient FE65 into cultured hippocampal neurons using adenovirus, we show that a complex including APP, FE65 and an additional protein is involved in neurite outgrowth at early stages of neuronal development. Both FE65 that is unable to interact with APP (PID2 mutants) or a WW mutant increased axon branching. Although the FE65 mutants did not affect total neurite output, both mutants decreased axon segment length, consistent with an overall slowing of axonal growth cones. FE65 mutants did not alter the localization of either APP or FE65 in axonal growth cones, suggesting that the effects on neurite outgrowth are achieved by alterations in local complex formation within the axonal growth cone. 相似文献
998.
999.
Suppression of mouse skin tumor promotion and induction of apoptosis in HL-60 cells by Alpinia oxyphylla Miquel (Zingiberaceae) 总被引:3,自引:0,他引:3
There have been considerable efforts to search for naturally occurring
substances for the intervention of carcinogenesis. Many components from
dietary or medicinal plants have been identified that possess substantial
chemopreventive properties. An example is curcumin (Curcuma longa Linn.,
Zingiberaceae), which has been shown to inhibit tumor promotion in
experimental carcinogenesis. Alpinia oxyphylla Miquel, another plant of the
ginger family used in oriental herbal medicine, contains diarylheptanoids
whose structures are analogous to that of curcumin. In the present study,
we have tested A.oxyphylla for its ability to suppress tumor promotion.
Thus, topical application of the methanolic extract of dried fruits of
A.oxyphylla significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate
(TPA)-induced skin tumor promotion as well as ear edema in female ICR mice.
In another study, treatment of HL-60 cells with the methanolic extract of
A.oxyphylla significantly reduced the viability of the cells and also
inhibited DNA synthesis. Microscopic examination of the treated cells
showed characteristic morphology of apoptosis. Furthermore, cells treated
with the extract of A.oxyphylla exhibited internucleosomal DNA
fragmentation in time- and concentration-dependent manners. TPA- stimulated
generation of superoxide anion in differentiated HL-60 cells was also
blunted by A.oxyphylla. Taken together, these findings suggest that
A.oxyphylla possesses potential chemopreventive and antitumorigenic
activities.
相似文献
1000.
M W Oberle C N Shapiro A P Lanier 《Public health reports (Washington, D.C. : 1974)》1997,112(1):63-65
OBJECTIVE: To determine the prevalence of testing for hepatitis B virus (HBV) infection in the clinical management of primary liver cancer (hepatocellular carcinoma). METHODS: The authors reviewed the records of 78 patients treated for hepatocellular carcinoma in hospitals in the Puget Sound area in 1988 and early 1989 and reviewed all 1990 U.S. death certificates on which primary liver cancer was listed. RESULTS: The records of 50 (64%) of 78 hepatocellular carcinoma patients contained no evidence that the patient''s hepatitis B surface antigen (HBsAg) status had been determined. In addition, of 4353 people who died in 1990 for whom the diagnosis of primary liver cancer was listed on the death certificate, HBV infection was also listed for only 136 (3%), much less than expected based on case series. CONCLUSIONS: Many patients with hepatocellular carcinoma are not tested for HBV infection, suggesting that their close contacts are also not evaluated for HBV infection and the need for vaccination. Hepatitis B vaccination of close personal contacts of HBV-infected hepatocellular carcinoma patients is an important strategy for preventing HBV transmission. 相似文献