全文获取类型
收费全文 | 191篇 |
免费 | 9篇 |
专业分类
儿科学 | 3篇 |
妇产科学 | 1篇 |
基础医学 | 56篇 |
临床医学 | 11篇 |
内科学 | 27篇 |
皮肤病学 | 2篇 |
神经病学 | 48篇 |
特种医学 | 1篇 |
外科学 | 17篇 |
预防医学 | 13篇 |
眼科学 | 1篇 |
药学 | 14篇 |
中国医学 | 1篇 |
肿瘤学 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 9篇 |
2012年 | 8篇 |
2011年 | 17篇 |
2010年 | 5篇 |
2009年 | 9篇 |
2008年 | 10篇 |
2007年 | 15篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 16篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1973年 | 1篇 |
1971年 | 5篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有200条查询结果,搜索用时 15 毫秒
1.
Cellular distribution of the new growth factor Pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues 总被引:7,自引:0,他引:7
J. M. Vanderwinden P. Mailleux S. N. Schiffmann J. J. Vanderhaeghen 《Anatomy and embryology》1992,186(4):387-406
Summary Pleiotrophin (PTN), also known as HBGAM, belongs to an emerging cytokine family unrelated to other growth factors. We report here the first comprehensive study using in situ hybridization on the cellular distribution of this new heparin-binding growth factor mRNA in rat tissues. PTN mRNA was developmentally expressed in many — but not all — neuroectodermal and mesodermal lineages, whilst no PTN mRNA was detected in endoderm, ectoderm and trophoblast. PTN mRNA was found in the nervous system throughout development, with a post-natal peak of expression. In the adult nervous system, significant expression persisted in hippocampal CA1 pyramidal neurons and in cortical neurons, but also in different non-neuronal cells types in various locations (olfactory nerve, cerebellar astrocytes, pituicytes, Schwann cells surrounding the neurons in sensory ganglia). PTN mRNA was also found during development in the mesenchyme of lung, gut, kidney and reproductive tract, in bone and cartilage progenitors, in dental pulp, in myoblasts, and in several other sites. Expression was differently regulated in each location, but usually faded around birth. In the adult, PTN mRNA was still present in the meninges, the iris, the Leydig cells of the testis and in the uterus. PTN mRNA was also strongly expressed in the basal layers of the tongue epithelium, which is the only epithelium and ectodermal derivative to express PTN mRNA, and this only after birth. PTN is known to be a growth factor for perinatal brain neurons and a mitogen for fibroblasts in vitro. Recently, trophic effects on epithelial cells and a role as a tumour growth factor have been reported. The mechanisms of regulation and the functions of PTN are however still uncertain. Its expression pattern during development suggests important roles in growth and differentiation. Moreover, the presence of PTN mRNA in several adult tissues and the up-regulation of PTN mRNA expression in the gravid uterus indicate that PTN also has physiological functions during adulthood. 相似文献
2.
J M Vanderwinden P Mailleux S N Schiffmann J J Vanderhaeghen M H De Laet 《The New England journal of medicine》1992,327(8):511-515
BACKGROUND. Hypertrophic pyloric stenosis is a common infantile disorder characterized by enlarged pyloric musculature and gastric-outlet obstruction. Its physiopathologic mechanism is not known, but a defect in pyloric relaxation (pylorospasm) has been postulated. Nitric oxide is a mediator of relaxation in the mammalian digestive tract, raising the possibility that pylorospasm could be caused by a defect in nitric oxide production. Since neuronal nitric oxide synthase and NADPH diaphorase are identical, we used the NADPH diaphorase histochemical reaction to study the distribution of nitric oxide synthase in pyloric tissue from patients with infantile hypertrophic pyloric stenosis. METHODS. We studied pyloric tissue from nine infants with infantile hypertrophic pyloric stenosis and seven control infants and children. Cryostat sections were processed for NADPH diaphorase histochemical analysis. A polyclonal tau antiserum was used to identify the enteric nervous system by immunohistochemical methods. RESULTS. NADPH diaphorase activity was restricted to the enteric nervous system and blood vessels. In the pyloric tissues from the control patients, intense diaphorase activity was present in the nerve fibers of the circular musculature, in the neurons and nerve bundles of the myenteric plexus, and in some nerve fibers of the longitudinal musculature. In the pyloric tissues from patients with infantile hypertrophic pyloric stenosis, the enteric nerve fibers in the hypertrophied circular musculature were enlarged and distorted and did not contain diaphorase activity, whereas the activity in the myenteric plexus and the longitudinal musculature was preserved. CONCLUSIONS. We suggest that a lack of nitric oxide synthase in pyloric tissue is responsible for pylorospasm in infantile hypertrophic pyloric stenosis. 相似文献
3.
4.
Serge Alain Sadeuh-Mba Ma?l Bessaud Denis Massenet Marie-Line Joffret Marie-Claire Endegue Richard Njouom Jean-Marc Reynes Dominique Rousset Francis Delpeyroux 《Journal of clinical microbiology》2013,51(3):759-770
Human enteroviruses (HEVs) are endemic worldwide and among the most common viruses infecting humans. Nevertheless, there are very limited data on the circulation and genetic diversity of HEVs in developing countries and sub-Saharan Africa in particular. We investigated the circulation and genetic diversity of HEVs among 436 healthy children in a limited area of the far north region of Cameroon in 2008 and 2009. We also characterized the genetic biodiversity of 146 nonpolio enterovirus (NPEV) isolates obtained throughout the year 2008 from stool specimens of patients with acute flaccid paralysis (AFP) in Cameroon, Chad, and Gabon. We found a high rate of NPEV infections (36.9%) among healthy children in the far north region of Cameroon. Overall, 45 different HEV types were found among healthy children and AFP patients. Interestingly, this study uncovered a high rate of HEVs of species C (HEV-C) among all typed NPEVs: 63.1% (94/149) and 39.5% (49/124) in healthy children and AFP cases, respectively. Besides extensive circulation, the most prevalent HEV-C type, coxsackievirus A-13, featured a tremendous intratypic diversity. Africa-specific HEV lineages were discovered, including HEV-C lineages and the recently reported EV-A71 “genogroup E.” Virtually all pathogenic circulating vaccine-derived polioviruses (cVDPVs) that have been fully characterized were recombinants between oral poliovaccine (OPV) strains and cocirculating HEV-C strains. The extensive circulation of diverse HEV-C types and lineages in countries where OPV is massively used constitutes a major viral factor that could promote the emergence of recombinant cVDPVs in the Central African subregion. 相似文献
5.
6.
Julien Lamontagne élise Jalbert-Arsenault émilie Pepin Marie-Line Peyot Neil B. Ruderman Christopher J. Nolan Erik Joly S.R. Murthy Madiraju Vincent Poitout Marc Prentki 《Diabetes》2013,62(6):2122-2129
Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity. We assessed glucose homeostasis by hyperinsulinemic-euglycemic and hyperglycemic clamp studies and energy expenditure by indirect calorimetry and biotelemetry in male Wistar and obese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazone (30 mg/kg). In vivo insulin secretion during clamped hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration. Insulin clearance was slightly increased in Wistar but not in ZDF rats. Insulin sensitivity in Wistar rats assessed by the hyperinsulinemic-euglycemic clamp was minimally affected by pioglitazone at this early time point. Pioglitazone also reduced energy expenditure in Wistar rats without altering respiratory exchange ratio or core body temperature. Glucose-induced insulin secretion (GIIS) and oxygen consumption were reduced by pioglitazone in isolated islets and INS832/13 cells. In conclusion, pioglitazone acutely induces whole-body metabolic slowing down and reduces GIIS, the latter being largely independent of the insulin-sensitizing action of the drug. The results suggest that pioglitazone has direct metabolic deceleration effects on the β-cell that may contribute to its capacity to lower insulinemia and antidiabetic action.Major drugs developed to treat type 2 diabetes aim at either increasing insulin secretion or reducing insulin resistance (1–4). Two classes of insulin-sensitizing agents are currently used, the biguanides (metformin) and the thiazolidinediones (TZDs), of which the only one still recommended for use in some countries is pioglitazone (5). TZDs are peroxisome proliferator–activated receptor-γ (PPARγ) agonists. They stimulate adipocyte differentiation, relieving other tissues from fat excess, thereby reducing their resistance to insulin (6,7). The beneficial effects of TZDs are not limited to increased insulin sensitivity and also include preservation of β-cell function (8). It is thought that the beneficial effect of TZDs on β-cell function in vivo is indirect and occurs via a relief of the need for insulin hypersecretion because of their insulin sensitizing action. We should, however, consider the possibility that the classical antidiabetic insulin sensitizers, pioglitazone and metformin, might also have beneficial effects on glucose homeostasis via direct reduction of insulin hypersecretion independently of insulin resistance.We previously demonstrated in vitro that pioglitazone acutely slows down glucose and lipid metabolism in the β cell and inhibits glucose-induced insulin secretion (GIIS) primarily at submaximal and much less at maximal glucose concentrations (right shift in the glucose dose response) via a PPARγ-independent mechanism (9). These acute effects of pioglitazone are likely attributable to complex I inhibition of the electron transport chain (10) and involve reduced glucose oxidation, decreased ATP levels, and increased AMPK activation (9). Interestingly, metformin causes similar effects (J.L. and M.P., unpublished data). Hence, we proposed the novel concept of “metabolic deceleration” as a mode of action of some antidiabetic drugs and suggested that the action of pioglitazone to reduce glucose metabolism and insulin secretion in the β-cell may partly explain its beneficial effects (9). The concept that metabolic deceleration protects the β-cell from both oxidative and endoplasmic reticulum stress has recently been reviewed (11,12).In the current study we performed in vivo experiments in normal Wistar and obese Zucker diabetic fatty (ZDF) rats to better understand how acute treatment with pioglitazone alters glucose homeostasis, with particular focus on how it reduces hyperinsulinemia. The following questions were asked: 1) Can we confirm in vivo our previous in vitro findings in isolated rat islet and β-cell line that pioglitazone acutely reduces insulin secretion? 2) Is this acute effect of pioglitazone on insulin secretion independent of its effects on insulin sensitivity? and 3) Does pioglitazone acutely slow down whole-body energy metabolism? 相似文献
7.
Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death 总被引:22,自引:0,他引:22
El-Assaad W Buteau J Peyot ML Nolan C Roduit R Hardy S Joly E Dbaibo G Rosenberg L Prentki M 《Endocrinology》2003,144(9):4154-4163
We have proposed the "glucolipotoxicity" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia. 相似文献
8.
Aurelien?Venara Juliette?Podevin Philippe?Godeberge Yann?Redon Marie-Line?Barussaud Igor?Sielezneff Michel?Queralto Cecile?Bourbao Anne?Chiffoleau Paul?A?LehurEmail author 《International journal of colorectal disease》2018,33(10):1479-1483
Purpose
Little is presently known on the impact of device type for Doppler-guided hemorrhoidal artery ligation/mucopexy (DGHAL) or circular stapled hemorrhoidopexy (CSH) when a surgical treatment is considered for hemorrhoidal disease (HD). In this study, we aimed to compare the outcome in terms of adverse events and recurrence rate, of patients included in the multicenter LigaLongo RCT (ClinicalTrials.gov NCT01240772) according to the type of devices used.Methods
In the DGHAL arm (N?=?193), the procedure was done with transanal hemorrhoidal dearterialization (THD)? (THD, Correggio, Italy) (104 patients) and with HAL-RAR? (Agency for Medical Innovations (AMI) GmbH, Feldkirch, Austria) (89 patients). In the CSH arm (N?=?184), procedure for prolapse and hemorrhoids (PPH)-03? (Ethicon Endo-Surgery, Cincinnati OH) and hemorrhoidopexy and prolapse (HEM)? (Covidien, Inc.) staplers were used in respectively 106 and 78 cases. Surgery-related morbidity at 90 postoperative days (POD) based on the Clavien-Dindo procedure-related complication score and clinical outcome in terms of recurrence and reoperation rate at 12 postoperative months (POM) was collected.Results
Three hundred and seventy-seven patients were randomized according to HD grade. In the DGHAL arm, the number of ligations and mucopexies was higher in the AMI group (p?<?0.0001); at 90 POD, the overall morbidity was similar between the two groups. In the CSH arm, donut sizes were similar; at 90 POD, the PPH group had a higher risk of postoperative grade 1 morbidity (anal urgency or incontinence) compared to the HEM group (p?=?0.003). At 12 POM, no statistical difference was found between the two groups of each arm in terms of grade III recurrence or reoperation.Conclusion
Postoperative morbidity and outcome at 1 year were similar regardless of the type of devices used. These findings suggest that device type has little impact on HD treatment results.Trial registration
clinicaltrials.gov—Identifier NCT012407729.
10.
Tifenn Clément Jeong B. Lee Aleksandra Ichkova Beatriz Rodriguez-Grande Marie-Line Fournier Justine Aussudre Michael Ogier Elizabeth Haddad Frederic Canini Muriel Koehl Djoher Nora Abrous Andre Obenaus Jerome Badaut 《Glia》2020,68(3):528-542
Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long-term structural alterations following jmTBI. 相似文献