全文获取类型
收费全文 | 47087篇 |
免费 | 2916篇 |
国内免费 | 374篇 |
学科分类
医药卫生 | 50377篇 |
出版年
2023年 | 316篇 |
2022年 | 922篇 |
2021年 | 1547篇 |
2020年 | 718篇 |
2019年 | 1033篇 |
2018年 | 1303篇 |
2017年 | 1038篇 |
2016年 | 1392篇 |
2015年 | 1870篇 |
2014年 | 2249篇 |
2013年 | 2698篇 |
2012年 | 4028篇 |
2011年 | 4031篇 |
2010年 | 2276篇 |
2009年 | 1999篇 |
2008年 | 2986篇 |
2007年 | 2783篇 |
2006年 | 2603篇 |
2005年 | 2455篇 |
2004年 | 2055篇 |
2003年 | 1834篇 |
2002年 | 1655篇 |
2001年 | 920篇 |
2000年 | 817篇 |
1999年 | 662篇 |
1998年 | 350篇 |
1997年 | 261篇 |
1996年 | 215篇 |
1995年 | 186篇 |
1994年 | 195篇 |
1993年 | 157篇 |
1992年 | 231篇 |
1991年 | 221篇 |
1990年 | 244篇 |
1989年 | 201篇 |
1988年 | 183篇 |
1987年 | 183篇 |
1986年 | 150篇 |
1985年 | 141篇 |
1984年 | 135篇 |
1983年 | 111篇 |
1982年 | 116篇 |
1981年 | 140篇 |
1980年 | 97篇 |
1979年 | 74篇 |
1978年 | 70篇 |
1977年 | 55篇 |
1976年 | 43篇 |
1975年 | 46篇 |
1974年 | 43篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献2.
A. Nakao H. Toyokawa A. Tsung M. A. Nalesnik D. B. Stolz J. Kohmoto A. Ikeda K. Tomiyama T. Harada T. Takahashi R. Yang M. P. Fink K. Morita A. M. K. Choi N. Murase 《American journal of transplantation》2006,6(10):2243-2255
Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury. 相似文献
3.
Sung Woo Lee Sung Hyuk Choi Yunsik Hong Wanbae Kim 《European journal of emergency medicine》2006,13(2):117-118
Generally, a computed tomography scan is conducted for the diagnosis of stroke in the emergency department, because these scans are easier and faster in the detection of stroke. If there are no signs of hemorrhage on computed tomography scan, an ischemic stroke is diagnosed and treated accordingly. A magnetic resonance imaging scan may be taken in order to verify ischemic stroke. This process may lead to improper treatment and is time consuming. To address this situation, case studies are presented in which magnetic resonance imaging diffusion-weighted imaging and gradient recalled echo were performed to detect hemorrhagic and ischemic stroke and particularly, subarachnoid hemorrhage, which is undetectable with a computed tomography scan. 相似文献
4.
Sami S Zoghbi H Umesha Shetty Masanori Ichise Masahiro Fujita Masao Imaizumi Jeih-San Liow Jay Shah John L Musachio Victor W Pike Robert B Innis 《Journal of nuclear medicine》2006,47(3):520-527
18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function. 相似文献
5.
6.
This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized
by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment
and the belief that PE is a normal part of aging, that it has no effective treatment, or that it will resolve itself, few
men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods;
desensitizing drugs; off-label use of antidepressants, phosphodiesterase type 5 inhibitors, or à-blockers), the majority of
men with PE are not satisfied with their results. New pharmacologic drugs develped specifically for the treatment of PE are
undergoing evaluation in clinical trials. For example, recent clinical research studies have revealed on-demand administration
of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and
satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction
with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral
therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development
may provide benefits over those available. 相似文献
7.
Jay Magaziner Eleanor M. Simonsick T. Michael Kashner J. Richard Hebel 《Journal of clinical epidemiology》1988,41(11)
The present study evaluates the response comparability between 361 elderly hip fracture patients admitted from the community to seven Baltimore area hospitals between 1984 and 1986 and interviewer selected proxies on items pertaining to patients' pre-fracture health and functional status. Agreement across items ranges from very poor to good and varies with respect to the health or functional area assessed. Proxies tend to overestimate patient disability relative to the patients themselves, especially with regard to capacity to perform instrumental activities of daily living. Although proxies who report the greatest contact with patients respond most comparably to the patients, when they do disagree, proxies with the greatest patient contact tend to overestimate patient disability. The authors suggest that attention to item construction and phrasing may improve response comparability. 相似文献
8.
The morbidity and mortality conference (M&MC) appears to have sprung from the efforts of physicians to improve practice through the examination of medical errors and bad outcomes. The modern M&MC has had limited examination (and almost none outside surgery and anesthesia), but may be straying from the precepts from which it evolved. Learning from one's errors is important, but confronting them is difficult and is particularly delicate when done in conference. If the effort is successful, it can serve as a model. If unsuccessful, it can instead convey the lesson that attempting to learn from error is at best unproductive and at worst unpleasant. Thus, the M&MC is a double-edged sword, and particular attention should be given to the way that it is conducted. The authors review the historical roots and current literature on the M&MC, discusses relevant literature on medical error, and offers a definition, guiding principles, and a set of guidelines for a modern internal medicine M&MC. The ideas are presented not as a blueprint, but rather to stimulate a debate on the merits of establishing a framework for a working model, in order to refocus on the tradition of self-analysis and critical thinking in a manner that is productive for all participants. 相似文献
9.
Critical size defect in the canine mandible. 总被引:3,自引:0,他引:3
Jin-Young Huh Byung-Ho Choi Byung-Young Kim Seoung-Ho Lee Shi-Jiang Zhu Jae-Hyung Jung 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2005,100(3):296-301
OBJECTIVE: The purpose of this study was to determine the minimum size defect in a canine mandible that would not spontaneously heal during the dog's natural life (the critical size defect). STUDY DESIGN: Sixteen adult female mongrel dogs underwent continuity resection on both sides of the mandible to create bilateral defects. In 8 dogs, mandibular defects ranging from 5 to 20 mm were created with periosteal resection. In the other 8 dogs, mandibular defects ranging from 30 to 60 mm were created preserving the periosteum. The dogs were then killed at 6 months and the defects examined using radiographs and histologic analysis. RESULTS: When the periosteum was removed, mandibular defects greater than 15 mm failed to heal across the entire defect. However, when the periosteum was preserved, mandibular defects needed to be greater than 50 mm in order to fail to heal. CONCLUSION: The critical size defect in a canine mandible model is 15 mm when the periosteum is removed and 50 mm when the periosteum is preserved. 相似文献
10.
Jay P. Brooks 《Transfusion》2005,45(S4):159S-171S
Efforts to make blood transfusion as safe as possible have focused on making the blood in the bag as disease-free as possible. The results have been dramatic, and the costs have been correspondingly high. Although blood services will have to continue to deal with emerging pathogens, efforts to reduce the transfusion of infectious agents presently posing a risk will require high incremental costs and result in only improvements of a small magnitude.
The other aspect of safe blood transfusion, the actual transfusion process performed primarily in hospitals, has been accorded considerably less interest. We should turn our attention to enhancing overall blood safety by focusing on improving the process of blood transfusion. Errors involving patient, specimen, and blood product identification put transfused patients at risk, increasing the mortality risk for some. Solutions that could improve the transfusion process are discussed as a focus of this article. 相似文献
The other aspect of safe blood transfusion, the actual transfusion process performed primarily in hospitals, has been accorded considerably less interest. We should turn our attention to enhancing overall blood safety by focusing on improving the process of blood transfusion. Errors involving patient, specimen, and blood product identification put transfused patients at risk, increasing the mortality risk for some. Solutions that could improve the transfusion process are discussed as a focus of this article. 相似文献