全文获取类型
收费全文 | 336篇 |
免费 | 81篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 1篇 |
基础医学 | 123篇 |
口腔科学 | 62篇 |
临床医学 | 49篇 |
内科学 | 58篇 |
皮肤病学 | 1篇 |
神经病学 | 11篇 |
特种医学 | 26篇 |
外科学 | 17篇 |
综合类 | 1篇 |
预防医学 | 23篇 |
眼科学 | 3篇 |
药学 | 29篇 |
1篇 | |
肿瘤学 | 16篇 |
出版年
2023年 | 2篇 |
2021年 | 13篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 7篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 7篇 |
2014年 | 20篇 |
2013年 | 12篇 |
2012年 | 23篇 |
2011年 | 16篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 9篇 |
2007年 | 18篇 |
2006年 | 11篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 6篇 |
2000年 | 11篇 |
1999年 | 10篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 12篇 |
1995年 | 6篇 |
1994年 | 13篇 |
1993年 | 5篇 |
1992年 | 12篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 13篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 13篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1973年 | 3篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1936年 | 1篇 |
1935年 | 1篇 |
排序方式: 共有425条查询结果,搜索用时 31 毫秒
1.
William V. Giannobile Rafaél A Hernandez Richard D. Finkelman Susan Ryarr Christopher P. Kiritsy Mark D'Andrea Samuel E. Lynch 《Journal of periodontal research》1996,31(5):301-312
Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) in combination have previously been shown to enhance periodontal regeneration. The objective of this study was to further characterize the biological effects of this combination of growth factors in non-human primates and compare the effects to those of each growth factor individually. Ligature-induced periodontitis was initiated in 10 cynomolgus monkeys. After periodontal lesions were established, surgery was performed, and either a methylcellulose gel vehicle or vehicle containing 10 μg each of either PDGF-BB, IGF-I or both PDGF-BB and IGF-I was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after treatment and the extent of periodontal regeneration was assessed by histomorphometry. At both 4 and 12 wk vehicle-treated lesions generally revealed minimal osseous defect fill (ODF) (8.5±2.1% and 14.5±5.7%, respectively) and new attachment (NA) (34.1±5.2% and 26.6±10.5%, respectively). IGF-I treatment did not significantly alter healing compared to vehicle in any parameter at both 4 and 12 wk. PDGFBB-treated sites exhibited significant (p<0.05) regeneration of NA (69.6±12.0%) at 12 wk; trends for PDGF-BB treatment effect were also observed in other parameters at 4 and 12 wk. although these increases were not statistically significant. Treatment with PDGF-BB/IGF-I resulted in 21.6±5.1 % and 42.5±8.3% ODF at 4 and 12 wk, respectively, and 64.1±7.7% and 74.6±7.4% NA at 4 and 12 wk, respectively (all significantly greater than vehicle, p<0.05). The results from this study demonstrated that: 1) IGF-1 alone at the dose tested did not significantly alter periodontal wound healing; 2) PDGF-BB alone significantly stimulated NA, with trends of effect on other parameters; and 3) the PDGF-BB/IGF-I combination resulted in significant increases in NA and ODF above vehicle at both 4 and 12 wk. 相似文献
2.
3.
4.
Samuel E. Lynch DMD DMSc ; Stephen B. Trippel MD ; Richard D. Finkelman DDS PhD ; Rafael A. Hernandez DMD ; Christopher P. Kiritsy BA ; Harry N. Antoniades PhD 《Wound repair and regeneration》1994,2(3):182-190
The combination of insulin-like growth factor-I and platelet-derived growth factor-BB has previously been shown to stimulate healing of soft tissue wounds and the formation of bone and ligament around teeth. The purpose of the present study was to evaluate the effects of platelet-derived growth factor-BB and insulin-like growth factor-I individually and in combination on the healing of osseous wounds. Four standardized cortical wounds were created in each tibia of 11 adult Yucatan miniature pigs. The wounds in one tibia per animal were treated with either purified recombinant human insulin-like growth factor-I, platelet-derived growth factor-BB, or both in a methylcellulose gel. The wounds in each contralateral tibia received placebo gel alone. Coded serial sections of each wound were evaluated by computer-aided histomorphometry 21 days after surgery. The area and perimeter of the newly formed mineralized callus, the thickness of the total callus, and the percentage of mineralized tissue within the callus were significantly increased compared with the values of matched controls only in wounds treated with a combination of insulin-like growth factor-I and platelet-derived growth factor-BB. No significant differences in the measured parameters of callus formation were found in wounds treated with either insulin-like growth factor-I or platelet-derived growth factor-BB alone. Cartilage was present only in sites treated with insulin-like growth factor-I alone. These results suggest that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I stimulates bone formation in wounds in long bones of adult animals and that these growth factors act via different pathways during the repair process. 相似文献
5.
Knut A. Selvig Ulf M. E. Wikesjö Gary C. Bogle Richard D. Finkelman 《Journal of clinical periodontology》1994,21(6):380-385
Abstract. Effects of a topically applied growth factor combination on fibroblast migration, collagen fiber formation and bone regeneration were studied in standardized periodontal defects in 4 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and into the dentin of maxillary and mandibular teeth. Collagen sponges, impregnated with 200 ng insulin-like growth factor II, 20 ng basic fibroblast growth factor and 6 ng transforming growth factor beta 1 were fitted to defects randomly in right or left quadrants and the flaps repositioned and sutured. Contralateral control defects received the collagen with vehicle only. Experimental procedures were staggered to allow observations of healing 3, 7, 10, and 14 days after surgery. Histometric analysis showed no differences in fibroblast and collagen density between control and growth factor defects. Bone regeneration was significantly greater in control than in growth factor defects 10 and 14 days after surgery. The rate of healing generally appeared more affected by intra-dog variations or procedural variations than by the growth factor combination. 相似文献
6.
Trang T. Duong Joanne St. Louis Joseph J. Gilbert Fred D. Finkelman Gill H. Strejan 《Journal of neuroimmunology》1992,36(2-3)
SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE. 相似文献
7.
Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis. 总被引:8,自引:10,他引:8
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G D Miralles M Y Stoeckle D F McDermott F D Finkelman H W Murray 《Infection and immunity》1994,62(3):1058-1063
In experimental Leishmania donovani infection in BALB/c mice, initial susceptibility gives way to T-cell-dependent acquired resistance and eventual control over visceral infection. Since various cytokines appear to underlie the host response to Leishmania infection, we examined infected liver tissue for gene expression of cytokines associated with Th1 (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]) and Th2 cells (IL-4 and IL-10). By Northern (RNA) blot analysis, only IFN-gamma mRNA expression was detected in livers of infected euthymic mice. To determine whether activation of Th1 cells develops selectively in this model, qualitative PCR analysis was used. These results indicated that mRNAs for IFN-gamma, IL-2, IL-4, and IL-10 were all induced by L. donovani infection. The potentially negative Th2 cell-associated response did not appear to play a functional role, however, since resistance was acquired, anti-IL-4 monoclonal antibody treatment did not accelerate control over visceral infection, and serum immunoglobulin E levels remained low. As judged by PCR analysis, IL-4 and IL-10 mRNAs were also expressed under three other conditions without apparent effect: in naive euthymic mice treated with IL-2, which induces leishmanicidal activity; in rechallenged immune mice, which resist reinfection; and in nude mice, which fail to control L. donovani. These results suggest that, like other Leishmania species, L. donovani infection may trigger a potentially suppressive Th2 cell-associated cytokine response. However, in T-cell-intact mice able to control L. donovani, this response either is insufficient to influence outcome or more likely is overshadowed by the Th1 cell response. 相似文献
8.
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
9.
Schistosoma japonicum-infected mice show reduced hepatic fibrosis and eosinophilia and selective inhibition of interleukin-5 secretion by CD4+ cells after treatment with anti-interleukin-2 antibodies.
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A W Cheever Y Xu A Sher F D Finkelman T M Cox J G Macedonia 《Infection and immunity》1993,61(4):1288-1292
Schistosoma japonicum-infected mice were injected with antibodies to interleukin-2 (IL-2) and/or IL-2 receptor to clarify the role of IL-2 on the granulomatous reaction around schistosome eggs in the liver. Granulomas were of normal or slightly increased size in animals subjected to IL-2 blockade, but hepatic fibrosis was markedly decreased in treated animals 10 weeks after infection. Anti-IL-2 treatment significantly decreased the in vitro secretion of IL-5 by antigen-stimulated spleen cells, and peripheral eosinophilia and tissue eosinophilia were diminished. Secretion of IL-2, IL-4, and gamma interferon was unaffected. Our results indicate that IL-2 is not an essential determinant of granuloma size in S. japonicum-infected mice but that, as in Schistosoma mansoni infection, the development of hepatic fibrosis is critically dependent on IL-2 levels and granuloma size and hepatic fibrosis are differentially regulated. 相似文献
10.
Zimmermann N Doepker MP Witte DP Stringer KF Fulkerson PC Pope SM Brandt EB Mishra A King NE Nikolaidis NM Wills-Karp M Finkelman FD Rothenberg ME 《American journal of respiratory cell and molecular biology》2005,32(5):428-435
Asthma is a complex inflammatory pulmonary disorder that is on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in the pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known to be involved in epithelial differentiation but not allergic disease. In situ hybridization revealed induction of SPRR2 signal in a subset of bronchial epithelial cells and mononuclear cells associated with inflammation after allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression was significantly decreased in IL-13-deficient mice. Studies in gene-targeted mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we aimed to determine if the induction of SPRR2 by allergen was tissue specific. Notably, SPRR2 was markedly increased in the small intestine after induction of allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology. 相似文献