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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.
Defensins are small, cationic, cyclic peptides that are abundantly stored in granules of neutrophils. Defensins non-specifically interact with membranes by forming weakly ion-selective pores. Here we demonstrate immunolocalization of defensin-secreting cells in human brain. Defensins, secreted by activated granulocytes, apparently are not prevented by the blood-brain barrier (BBB) from diffusing across cerebral endothelium to penetrate the neuropil for a considerable distance from the granulocyte. This is in contrast to other neutrophil proteins like the granuleassociated enzyme elastase or the cytosolic protein MRP-14, which are strictly localized to the cytoplasm or granules of neutrophils. Thus, defensins, known chemokinetic and chemotactic molecules, display a unique distribution at BBB sites. © 1995 Wiley-Liss, Inc. 相似文献
3.
4.
G. Mumcu T. Ergun Y. Elbir E. Eksioglu-Demiralp S. Yavuz T. Atalay H. Direskeneli 《Journal of oral pathology & medicine》2005,34(1):13-16
Background: The aim of this study was to evaluate the effects of azithromycin on mucocutaneous manifestations, oral health and immune response in Behçet's disease (BD). Methods: Eight BD patients with active mucocutaneous symptoms were treated with azithromycin for 4 weeks. Oral health, clinical manifestations and in vitro interleukin (IL)‐12, interferon (IFN)‐γ, IL‐10 and monocyte chemotactic protein (MCP)‐1 responses were evaluated before and after treatment. Results: The number of folliculitic lesions, healing time of oral ulcers and scores of plaque indexes (PLIs) were lower after azithromycin treatment (P < 0.05). Scores of PLIs correlated positively with the healing time of oral ulcers (P = 0.02). Although a trend towards increased stimulated IL‐10 responses with azithromycin was observed, no statistically significant difference was found. Stimulated and unstimulated MCP‐1, IFN‐γ and IL‐12 responses were similar before and after treatment (P > 0.05). Conclusion: Azithromycin was observed to be effective in decreasing folliculitic lesions and fastening the healing time of oral ulcers in BD. 相似文献
5.
Luong Dong Cao Ishiwada Naruhiko Takeda Nobue Kohno Yoichi 《Pediatrics international》2004,46(4):419-424
BACKGROUND: Haemophilus influenzae (H. influenzae) is the most frequent bacterial pathogen of respiratory tract infections in children. Detection of antimicrobial susceptibility of H. influenzae is necessary for institution of appropriate antibiotic treatments. METHODS: A total of 281 strains of H. influenzae isolated from sputum samples of 281 pediatric patients with respiratory tract infections were recruited for study. Antibiotic susceptibility was determined by assessing minimum inhibitory concentrations (MIC) of antimicrobial agents. MIC were measured by utility of Agar dilution susceptibility test. RESULTS: Of the total, 38 (13.5%) strains produced beta-lactamase (BLP), 56 (19.9%) strains were beta-lactamase non-producing, ampicillin resistant (BLNAR). The overall resistant proportion to ampicillin was 33.4%. The data indicated that sulbactam/ampicillin, cefotaxime, ceftriaxone and cefditoren are effective against BLP strains. In addition, a high prevalence of BLNAR H. influenzae strains was identified, with an overall isolation rate of 19.9%. Those strains mainly demonstrated intermediate level to ampicillin (ampicillin-MIC = 3.13 micro g/mL for most of BLNAR strains). However, antimicrobial activities of cefotaxime, ceftriaxone and cefditoren against those strains were slightly diminished. Recovery rate of BLP strains was varied by years, peaking at 19.5%. In particular, a trend of yearly increase in frequency of BLNAR strains was observed. CONCLUSION: Frequency of BLNAR strains causing respiratory infections has been dramatically increasing, which can diminish antibiotic activities of not only ampicillin but also of some cephems. 相似文献
6.
医院感染常见细菌分布与耐药性分析 总被引:6,自引:0,他引:6
目的了解细菌分布及常见细菌的耐药性。方法回顾性分析某院2000—2004年临床标本分离的细菌及其耐药性监测结果。结果1439株细菌中,革兰阳性菌456株(31.69%),以凝固酶阴性表皮葡萄球菌为多,达206株(45.18%),其次为金黄色葡萄球菌92株(20.18%);两种葡萄球菌的耐药率相似,对万古霉素耐药率均为0。革兰阴性菌983株,前5位依次为肠杆菌属346株(35.20%),克雷伯菌属164株(16,68%),铜绿假单胞菌155株(15.77%),埃希菌属101株(10.27%),变形杆菌属94株(9.56%);前5位革兰阴性菌对常用抗菌药物的耐药性以半合成青霉索较明显,铜绿假单胞菌的耐药性较突出。结论应高度重视细菌变迁和耐药性监测,提高抗菌药物合理应用水平。 相似文献
7.
M.E. Houston L.H. Kondejewski D.N. Karunaratne M. Gough S. Fidai R.S. Hodges R.E.W. Hancock 《Chemical biology & drug design》1998,52(2):81-88
One prominent class of cationic antibacterial peptides comprises the α-helical class, which is unstructured in free solution but folds into an amphipathic α-helix upon insertion into the membranes of target cells. To investigate the importance of α-helicity and its induction on interaction with membranes, a series of peptides was constructed based on a hybrid of moth cecropin (amino acids 1-8) and bee melittin (amino acids 1-18) peptides. The new peptides were predicted to have a high tendency to form α-helices or to have preformed α-helices by virtue of construction of a lactam bridge between glutamate and lysine side-chains at positions i and i+ 4 at various locations along the primary sequence. In two examples where the use of lactam bridge constraints induced and stabilized α-helical structure in benign (aqueous buffer) and/or hydrophobic medium, there was a decrease in antibacterial activity relative to the linear counterparts. Thus the preformation of α-helix in solution was not necessarily beneficial to antimicrobial activity. In the one case where the lactam bridge did result in increased antibacterial activity (lower minimal inhibitory concentration values) it did not increase α-helical content in benign or hydrophobic medium. Broadly speaking, good activity of the peptides against Pseudomonas aeruginosa correlated best (r2= 0.88) with a helican parameter which was calculated as the induction of α-helix in α membrane-mimicking environment divided by the α-helix formation under benign conditions. Interestingly, the activity of the lactam bridge peptide constructs correlated in part with alterations in bacterial outer or cytoplasmic membrane permeability. 相似文献
8.
William J. Killoy 《Journal of clinical periodontology》1998,25(11):953-958
Abstract. Since the advent of a nondegradable controlled local delivery of antibiotics in 1979, several second generation systems have been developed. Second generation systems have attempted to improve on the early system. Chlorhexidine has been used effectively for over 30 years as an antiseptic. In the early 1970s, chlorhexidine gluconate was incorporated at 0.2% into mouthrinses in Europe and in 1986 it was incorporated at 0.12%, in a mouthrinse in the United States. Since these mouthrinses were effective in reducing the supragingival flora, had a high safety margin, and had no reported bacterial resistance, chlorhexidine offered a therapeutic advantage for a local delivery system. This system was developed and studied. This report will discuss this new biodegradable system containing chlorhexidine gluconate as the active agent (PerioChip®). Parmacokinetics of the system and a review of the multicenter studies in Europe and the United States are discussed. In these randomized clinical trials the chlorhexidine chip has been shown to enhance the effects of scaling and root planing. Chlorhexidine chip in conjunction with scaling and root planing, when compared to scaling and root planing alone, has shown significant improvement in probing pocket depth reduction, probing attachment level and bleeding on probing. This delivery system, in combination with scaling and root planing, has also resulted in significantly more probing depth reductions of 2 mm or more. The system is safe and efficacious. Placement of the chip is usually done in less than 1 min, it requires no retention system, biodegrades, and does not require a follow-up dental appointment. 相似文献
9.
I. V. Stupin A. I. Novokshonov A. M. Domborvskii G. G. Belous M. Yu. Ivanov 《Bulletin of experimental biology and medicine》1990,110(4):1407-1409
Department of Experimental Surgery, Interfaculty Laboratory Complex, and Department of Clinical Laboratory Diagnosis, Postgraduate Medical Faculty, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 413–145, October, 1990. 相似文献