首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   568篇
  免费   34篇
  国内免费   6篇
耳鼻咽喉   23篇
儿科学   12篇
妇产科学   10篇
基础医学   49篇
口腔科学   4篇
临床医学   57篇
内科学   249篇
神经病学   12篇
特种医学   37篇
外科学   46篇
综合类   2篇
预防医学   6篇
眼科学   29篇
药学   32篇
肿瘤学   40篇
  2023年   3篇
  2022年   7篇
  2021年   17篇
  2020年   5篇
  2019年   15篇
  2018年   12篇
  2017年   13篇
  2016年   8篇
  2015年   11篇
  2014年   14篇
  2013年   24篇
  2012年   31篇
  2011年   26篇
  2010年   17篇
  2009年   10篇
  2008年   27篇
  2007年   26篇
  2006年   27篇
  2005年   30篇
  2004年   32篇
  2003年   39篇
  2002年   34篇
  2001年   29篇
  2000年   34篇
  1999年   23篇
  1998年   4篇
  1997年   4篇
  1996年   2篇
  1995年   5篇
  1994年   2篇
  1993年   3篇
  1992年   10篇
  1991年   6篇
  1990年   5篇
  1989年   10篇
  1988年   3篇
  1987年   4篇
  1986年   5篇
  1985年   2篇
  1983年   4篇
  1981年   3篇
  1979年   4篇
  1978年   4篇
  1977年   2篇
  1974年   3篇
  1973年   1篇
  1971年   1篇
  1969年   2篇
  1947年   1篇
  1938年   1篇
排序方式: 共有608条查询结果,搜索用时 15 毫秒
1.
The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.  相似文献   
2.
3.
Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL.  相似文献   
4.
To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.  相似文献   
5.
6.
HLA-Bw54 (Bw22-J, J-1) Antigen in Juvenile Onset Diabetes Mellitus in Japan   总被引:2,自引:0,他引:2  
HLA—B8 and/or Bw15, associated with juvenile onset insulin-dependent diabetes mellitus (JDM) in Caucasians, have a very low frequency in the Japanese population. Thus, we were interested in investigating the association between JDM and HLA antigen in a Japanese population. Eighty-nine patients with JDM and 128 unrelated random controls were HLA-typed by the micro-lymphocytotoxicity test. The data revealed a significant, positive association between this type of diabetes mellitus and HLA-Bw54 (Bw22-J, J-1) antigen (Japanese-specific split antigen of HLA—Bw22).  相似文献   
7.
Objectives Describe contribution of laryngeal movement to pressure changes at the upper esophageal sphincter (UES) and the effect of aging on the swallowing function. Study Design Manofluorography on 56 nondysphagic adults divided into three age groups: the 21‐ to 31‐year‐old group (n = 32), the 61‐ to 74‐year‐old group (n = 12) and the 75‐ to 89‐year‐old group (n = 12). Analyses of the bolus transit time, the amplitudes and durations of pharyngeal pressures, the timing of a pressure fall at the UES and the laryngeal movements. Methods Intraluminal strain‐gauge sensors recorded pressure changes in the oropharynx, hypopharynx and the UES. Motion pictures of the videotapes were fed into a personal computer, and movements of the hyoid bone were measured in both the horizontal and vertical directions as an indication of laryngeal movement. Results In 26‐ and 70‐year‐old men with calcification of the thyroid cartilage, it was determined that the larynx and hyoid bone moved in consonance until the end of the rapid hyoid movements in both the superior and anterior directions. In the 21‐ to 31‐year‐old group, the magnitude of the pressure fall at the UES was maximal before or almost at the same time as the bolus arrival, in preparation for smooth passage of the bolus from the pharynx to the esophagus. The rapid superior movements of the hyoid bone started significantly early as compared with its anterior movements (P = .0001). The rapid anterior movements of the hyoid bone started simultaneously with the pressure fall at the UES. In the elderly, all segmental transit times were significantly increased. The timing of the pressure fall at the UES was significantly delayed and the UES pressure reached its minimum value after arrival of the bolus at the UES. The minimum pressure at the UES increased to a significantly positive value. The rapid anterior movements of the hyoid were significantly delayed, suggesting that this delay causes the delay in the pressure fall at the UES. Conclusions The rapid superior and anterior movements of the hyoid bone are considered to start at the same time as those of the larynx. In the young group, it is suggested that superior laryngeal movement protects the lower airway prior to the anterior laryngeal movement, causing the pressure fall at the UES to enable the passage of a bolus into the UES. In the elderly, smooth passage of the bolus from the pharynx to the esophagus is hindered and the system that prevents aspiration is rendered inefficient by changes in the swallowing pressures and laryngeal movements with aging.  相似文献   
8.
PURPOSE: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib. PATIENTS AND METHODS: We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. RESULTS: EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of NSCLC. In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P = .001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. CONCLUSION: EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers.  相似文献   
9.
10.
Nectin‐like molecule 4 (Necl‐4)/CADM4, a transmembrane cell–cell adhesion molecule with three Ig‐like domains, was shown to serve as a tumor suppressor, but its mode of action has not been elucidated. In this study, we showed that Necl‐4 interacted in cis with ErbB3 through their extracellular regions, recruited PTPN13 and inhibited the heregulin‐induced activation of the ErbB2/ErbB3 signaling. In addition, we extended our previous finding that Necl‐4 interacts in cis with integrin α6β4 through their extracellular regions and found that Necl‐4 inhibited the phorbol ester‐induced disassembly of hemidesmosomes. These results indicate that Necl‐4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号