全文获取类型
收费全文 | 135篇 |
免费 | 29篇 |
国内免费 | 7篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 1篇 |
基础医学 | 40篇 |
口腔科学 | 3篇 |
临床医学 | 15篇 |
内科学 | 31篇 |
特种医学 | 28篇 |
外科学 | 12篇 |
综合类 | 1篇 |
预防医学 | 10篇 |
药学 | 20篇 |
1篇 | |
肿瘤学 | 5篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 10篇 |
2014年 | 4篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 3篇 |
2010年 | 5篇 |
2009年 | 8篇 |
2008年 | 2篇 |
2007年 | 15篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有171条查询结果,搜索用时 15 毫秒
1.
2.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
3.
4.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
5.
艾叶油的呼吸系统药理研究-Ⅱ,抗过敏作用 总被引:9,自引:1,他引:9
目的:本文研究艾叶油的抗过敏作用。方法:采用致敏豚鼠气管SchultzDale 反应,组胺或氨甲酰胆碱引起的豚鼠气管收缩,大鼠被动皮肤过敏,5羟色胺引起的大鼠皮肤毛细血管通透性增强,豚鼠肺组织释放过敏性慢反应物质(SRSA) ,SRSA 收缩豚鼠回肠等试验。结果:艾叶油抑制致敏豚鼠气管SchultzDale 反应(IC50 :98 .6mg/L) ;100mg/L 明显降低组胺或氨甲酰胆碱引起的豚鼠气管收缩pD2 值;明显抑制大鼠被动皮肤过敏(ID50 :0 .22g/kg) 和5羟色胺引起的大鼠皮肤毛细血管通透性增强反应(ID50 :0 .52g/kg) ;抑制豚鼠肺组织释放SRSA(IC50 :49 .7mg/L) ;拮抗SRSA 对豚鼠回肠的收缩(IC50 :34 .9mg/L) 。结论:艾叶油具有抗过敏作用,对呼吸道过敏反应有保护作用,是其治疗支气管哮喘和慢性气管炎作用机制之一 相似文献
6.
CL Sanchez CS Biskup S Herpertz TJ Gaber CM Kuhn SH Hood FD Zepf 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(10)
The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research. 相似文献
7.
ST Hornby FD McDermott M Coleman Z Ahmed J Bunni D Bunting M Elshaer V Evans A Kimble M Kostalas G Page J Singh L Szczebiot S Wienand-Barnett A Wilkins O Williams P Newell Severn Peninsula Audit Research Collaborative 《Annals of the Royal College of Surgeons of England》2015,97(2):115-119
Background
Laparoscopic hernia repair is used widely for the repair of incisional hernias. Few case studies have focussed on purely ‘incisional’ hernias. This multicentre series represents a collaborative effort and employed statistical analyses to provide insight into the factors predisposing to recurrence of incisional hernia after laparoscopic repair. A specific hypothesis (ie, laterality of hernias as well as proximity to the xyphoid process and pubic symphysis predisposes to recurrence) was also tested.Methods
This was a retrospective study of all laparoscopic incisional hernias undertaken in six centres from 1 January 2004 to 31 December 2010. It comprised a comprehensive review of case notes and a follow-up using a structured telephone questionnaire. Patient demographics, previous medical/surgical history, surgical procedure, postoperative recovery, and perceived effect on quality of life were recorded. Repairs undertaken for primary ventral hernias were excluded. A logistic regression analysis was then fitted with recurrence as the primary outcome.Results
A total of 186 cases (91 females) were identified. Median follow-up was 42 months. Telephone interviews were answered by 115/186 (62%) of subjects. Logistic regression analyses suggested that only female sex (odds ratio (OR) 3.53; 95% confidence interval (CI) 1.39–8.97) and diabetes mellitus (3.54; 1–12.56) significantly increased the risk of recurrence. Position of the defect had no statistical effect.Conclusions
These data suggest an increased risk of recurrence after laparoscopic incisional hernia repair in females and subjects with diabetes mellitus. These data will help inform surgeons and patients when considering laparoscopic management of incisional hernias. We recommend a centrally hosted, prospectively maintained national/international database to carry out additional research. 相似文献8.
Charlotte Bradbury Kate Fletcher Yongzhong Sun Carl Heneghan Chris Gardiner Andrea Roalfe Pollyanna Hardy Debbie McCahon Gail Heritage Helen Shackleford FD Richard Hobbs David Fitzmaurice 《British journal of haematology》2020,188(6):962-975
Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81–11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients. 相似文献
9.
10.