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排序方式: 共有929条查询结果,搜索用时 31 毫秒
1.
Quantification of Basal and Stimulated ROS Levels as Predictors of Islet Potency and Function 总被引:2,自引:0,他引:2
B. Armann M. S. Hanson E. Hatch A. Steffen L. A. Fernandez 《American journal of transplantation》2007,7(1):38-47
We have developed a luminol-based assay using intact islets, which allows for quantification of reactive oxygen species (ROS). In addition, an index capable of characterizing metabolic and mitochondrial integrity prior to transplantation was created based on the capacity of islets to respond to high glucose and rotenone (mitochondrial respiratory chain complex I inhibitor) by production of ROS. To validate this assay, lipid peroxidation and antioxidative defense capacity were evaluated by detection of malondialdehyde (MDA) levels and glutathione peroxidase activity (GPx), respectively. Also, flow cytometric analyses of ROS (dihydroethidine), apoptosis (Annexin V, active caspases), necrosis (Topro3), and mitochondrial membrane potential (JC-1) were done in parallel to correlate with changes in luminol-measured ROS. ATP/ADP ratios were quantified by HPLC and the predictive value of ROS measurement on islet functional potency was correlated with capacity to reverse diabetes in a streptozotocin-induced diabetic NOD.scid mouse model as well as in human transplant recipients. Our data demonstrate that levels of ROS in islets correlate with the percentage of apoptotic cells and their functional potency in vivo. The ROS indices following glucose and rotenone exposure are indicative of metabolic potency and mitochondrial integrity and can be used as surrogate markers to evaluate the quality of islets prior to transplantation. 相似文献
2.
3.
L.E. Oostenbrug I.M. Nolte E. Oosterom G. van der Steege G.J. te Meerman H.M. van Dullemen J.P.H. Drenth D.J. de Jong K. van der Linde P.L.M. Jansen J.H. Kleibeuker 《Digestive and liver disease》2006,38(11):834-845
BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course. 相似文献
4.
Franoise Lepault Marie-Claude Gagnerault Christelle Faveeuw Herv Bazin Christian Boitard 《European journal of immunology》1995,25(6):1502-1507
The process of mononuclear cell extravasation from the blood into the islets of Langerhans in nonobese diabetic (NOD) mice is dependent on the expression of a set of molecules, most of which remain to be defined. The observation that vascular addressins are expressed in inflamed islets raises the issue of the involvement of one of their ligands, L-selectin, in the pathogenesis of autoimmune diabetes. Treatment of NOD females with Mel-14, an antibody specific for L-selectin, reduced the spontaneous development of both insulitis and diabetes. Pretreatment of diabetic donors with Mel-14 decreased the capacity of their splenocytes to transfer the disease. However, the treatment of recipients had no effect on the transfer of diabetes by untreated diabetogenic splenocytes. To reconcile these apparently conflicting results, we fractionated spleen T cells from diabetic mice according to L-selectin expression. Diabetogenic cells were found only in the L-selectin subpopulation. Thus, diabetogenic cells in adult mice share phenotypic characteristics with activated/memory cells, and enter the pancreas using L-selectin-independent migratory pathways. 相似文献
5.
目的:建立能反应自身免疫特点的1型糖尿病动物模型,为进一步研究该病发病机理奠定基础。方法:将16只NOD.Scid小鼠随机分为两组,实验组小鼠腹腔注射发病NOD小鼠脾细胞,对照组注射未发病NOD小鼠脾细胞;每日测定血糖和体重;当出现重度糖尿病临床表现时处死,其余小鼠细胞过继后10周处死,经组织学观察和细胞因子ELISA测定。结果:实验组小鼠发病率为8/8,对照组为0/8;胰岛炎性积分分别为2.5±0.2,0;实验组IL-2、IL-10、IFN-γ水平分别为60.7pg/ml、15.5pg/ml、20.2ng/ml,对照组为2.4pg/ml、17.5pg/ml、3.2ng/ml。结论:在NOD.Scid小鼠体内一次性过继发病NOD小鼠脾细胞后5~10周可成功建立1型糖尿病的小鼠模型。 相似文献
6.
Christelle Faveeuw Marie-Claude Gagnerault Fran?oise Lepault 《Clinical & developmental immunology》1994,3(4):273-282
Subpopulations of lymphoid cells were compared with respect to their ability to migrate into
peripheral lymphoid organs of nonobese diabetic (NOD) mice and various strains of control
mice. In short-term, in vivo homing studies, no major differences in the pattern of homing
of B and T cells were observed among all mouse strains studied. On the other hand, CD4
cells localized consistently more efficiently than CD8 cells in both PP and LN of adult NOD
and BALB/c mice, whereas both populations migrated roughly equivalently in LN of adult
DBA/2, CBA, and C57BL/6 mice. No age-dependent differences in the homing of CD4 and
CD8 cells were observed in BALB/c mice. On the contrary, in 2-week-old NOD mice, CD4
and CD8 cells migrated equally well. The preferential entry of CD4 cells in adult NOD and
BALB/c did not result from increased blood transit time of CD8 cells. On the other hand,
the preferential migration of CD8 cells was observed in the liver, whereas the two T-cell
subsets migrated equally well in the lungs. The differences in the homing characteristics of
CD4 and CD8 cells among NOD, BALB/c, and C57BL/6 mice were not related to
modifications in the level of expression of adhesion molecules such as MEL-14, LFA-1, and
Pgp-1. 相似文献
7.
Yuichi Takeoka Shao-Yuan Chen Richard L. Boyd Koichi Tsuneyama Nobuhisa Taguchi Shinji Morita Hisashi Yago Seishi Suehiro Aftab A. Ansari Leonard D. Shultz M. Eric Gershwin 《Clinical & developmental immunology》1997,5(2):79-89
It is widely accepted that the thymic microenvironment regulates normal thymopoiesis
through a highly coordinated and complex series of cellular and cytokine interactions. A direct
corollary of this is that abnormalities within the microenvironment could be of etiologic
significance in T-cell-based diseases. Our laboratory has developed a large panel of
monoclonal antibodies (mAbs) that react specifically with epithelial or nonepithelial
markers in the thymus. We have taken advantage of these reagents to characterize the
thymic microenvironment of several genetic strains of mice, including BALB/cJ,
C57BL/6J, NZB/BlnJ, SM/J, NOD/Ltz, NOD/Ltz-scid/sz, C57BL/6J-Hcph
me/Hcph me, and
ALY/NscJcl-aly/aly mice, and littermate control animals. We report herein that control
mice, including strains of several backgrounds, have a very consistent phenotypic profile
with this panel of monoclonal antibodies, including reactivity with thymic epithelial cells
in the cortex, the medulla and the corticomedullary junction, and the extracellular matrix.
In contrast, the disease-prone strains studied have unique, abnormal staining of thymic cortex
and medulla at both the structural and cellular levels. These phenotypic data suggest
that abnormalities in interactions between developing thymocytes and stromal cells characterize
disease-prone mice. 相似文献
8.
目的 进一步研究NOD小鼠T细胞应答改变机理。方法 用抗TCR抗体、ConA激活NOD小鼠胸腺细胞,分析TCR介导的信号通路的水平。结果 与Balb/c小鼠胸腺细胞相比,抗TCR抗体诱导的增殖应答较弱,与年龄及NOD胸腺CD4^ CD8^-和CD4^-CD8^ SP细胞有关;rIL-2能部分恢复对TCR抗体应答的缺乏。NOD小鼠对PMA IONO和PMA anti—TCR-mAb应答正常,但对anti-TCRmAb IONO应答缺乏。结论 与年龄有关的NOD小鼠胸腺细胞对TCR抗体应答的缺乏与T细胞激活时上游PKC信号通路的缺乏有关。 相似文献
9.
Immune-deficient SCID and NOD/SCID mice models as functional assays for studying normal and malignant human hematopoiesis 总被引:3,自引:0,他引:3
T. Lapidot Yfat Fajerman Orit Kollet 《Journal of molecular medicine (Berlin, Germany)》1997,75(9):664-673
Many events and requirements of the developmental program of human hematopoietic stem cells have not yet been discovered.
A major impediment has been the lack of an appropriate experimental system. At present the conditions for maintaining human
stem cells in vitro are not fully known. As a result within a short period the small stem cell pool is lost due to differentiation,
making it difficult to examine the correlation between these cells and their function in vivo. Most of our knowledge of hematopoietic
stem cells is from animal models in which purified stem cell canididates are assayed based on their functional ability to
rescue lethally conditioned recipients. The permanent correction of many genetic disorders of the hematopoietic system requires
efficient methods for introducing genes into stem cells in vitro. However, progress has been hindered by the absence of preclinical
models that assay the repopulating capacity of primitive human cells. In addition, the development of therapy for malignant
diseases also requires assays to identify the target leukemic stem cells based on their ability to initiate the disease. The
recent development of methods to transplant or implant both normal and leukemic cells into immune-deficient mice provides
the foundation for human stem cell assays. These models assay the repopulating capacity of primitive human cells and provide
an important approach to identify and characterize human stem cells, both normal and leukemic. This review focuses on the
development of functional assays for normal and leukemic human stem cells and on the new insights that these models are beginning
to provide on the organization of the human stem cell hierarchy.
Received: 27 January 1997 / Accepted: 3 April 1997 相似文献
10.
Decallonne B van Etten E Overbergh L Valckx D Bouillon R Mathieu C 《Journal of autoimmunity》2005,24(4):281-289
AIMS/HYPOTHESIS: Resistance of NOD thymocytes to apoptosis-inducing signals is restored by 1alpha,25-dihydroxyvitamin D3 (1alpha,25OH2D3), a therapy preventing diabetes in NOD mice. We studied whether modulation of thymocyte apoptosis is due to direct effects on thymic T lymphocytes or indirect effects via thymic dendritic cells, since both cell types constitute known targets for 1alpha,25OH2D3. METHODS AND RESULTS: Female NOD mice were treated with 1alpha,25OH2D3 (5microg/kg/2d) from 21 to 70 days. Vehicle-treated NOD and NOR mice served as controls. Analysis of thymic T lymphocytes from 1alpha,25OH2D3)-treated mice revealed a decrease in number of apoptosis-resistant CD4+CD8+ and CD4+CD8-HSA(high) T lymphocyte subsets, higher pro-apoptotic IL-2 and FasL, and lower anti-apoptotic Bclx-L mRNA expression levels. Thymic dendritic cells from 1alpha,25OH2D3-treated NOD mice had increased CD8alpha+FasL+ and CD80+/86+ expression compared to control NOD mice. In a syngeneic co-culture system of thymocytes and thymic dendritic cells, apoptosis levels were 20% higher only in co-cultures where both T cell- and dendritic cell-compartments originated from 1alpha,25OH2D3-treated mice. Activation-induced cell death-sensitivity in peripheral T lymphocytes was comparable to levels present in NOR mice, confirming better thymic selection in 1alpha,25OH2D3-treated mice. CONCLUSION/INTERPRETATION: We conclude that 1alpha,25OH2D3 needs both thymic T cell- and dendritic cell-compartments to exert its apoptosis-restorative effects in NOD thymocytes. 相似文献