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   267篇
  免费   20篇
  2023年   3篇
  2021年   10篇
  2020年   7篇
  2019年   8篇
  2018年   7篇
  2017年   5篇
  2016年   8篇
  2015年   8篇
  2014年   8篇
  2013年   19篇
  2012年   23篇
  2011年   29篇
  2010年   11篇
  2009年   20篇
  2008年   19篇
  2007年   16篇
  2006年   19篇
  2005年   9篇
  2004年   7篇
  2003年   10篇
  2002年   4篇
  2001年   3篇
  2000年   1篇
  1999年   1篇
  1998年   1篇
  1997年   2篇
  1996年   3篇
  1995年   3篇
  1994年   3篇
  1993年   2篇
  1992年   1篇
  1988年   1篇
  1986年   1篇
  1985年   1篇
  1984年   1篇
  1983年   2篇
  1982年   3篇
  1981年   3篇
  1980年   1篇
  1979年   1篇
  1977年   1篇
  1975年   1篇
  1974年   1篇
排序方式: 共有287条查询结果,搜索用时 421 毫秒
221.
Studies have evidenced that zinc metabolism is altered in presence of Down syndrome, and zinc seems to have a relationship with the metabolic alterations usually present in this syndrome. In this work, the Zn-related nutritional status of adolescents with Down syndrome was evaluated by means of biochemical parameters and diet. A case–control study was performed in a group of adolescents with Down syndrome (n = 30) and a control group (n = 32), of both sexes, aged 10 to 19 years. Diet evaluation was accomplished by using a 3-day dietary record, and the analysis was performed by the NutWin program, version 1.5. Antropometric measurements were performed for evaluation of body composition. The Zn-related nutritional status of the groups was evaluated by means of zinc concentration determinations in plasma and erythrocytes, and 24-h urinary zinc excretion, by using the method of atomic absorption spectroscopy. The diet of both groups presented adequate concentrations of lipids, proteins, carbohydrates, and zinc. The mean values found for zinc concentration in erythrocytes were 49.2 ± 8.5 μg Zn/g Hb for the Down syndrome group and 35.9 ± 6.1 μg Zn/g Hb for the control group (p = 0.001). The average values found for zinc concentration in plasma were 67.6 ± 25.6 μg/dL for the Down syndrome group and 68.9 ± 22.3 μg/dL for the control group. The mean values found for zinc concentration in urine were 244.3 ± 194.9 μg Zn/24 h for the Down syndrome group and 200.3 ± 236.4 μg Zn/24 h for the control group. Assessment of body composition revealed overweight (26.7%) and obesity (6.6%) in the Down syndrome group. In this study, patients with Down syndrome presented altered zinc levels for some cellular compartments, and the average zinc concentrations were low in plasma and urine and elevated in erythrocytes.  相似文献   
222.
Trypanosoma cruzi epimastigotes adhere in vivo to the luminal surface of their triatomid vector digestive tract by molecular mechanisms, as yet, unknown. Here, we show that the administration of 0.5 microM epimastigote major surface glycoinositolphospholipids (GIPLs) to the infected bloodmeal inhibits up to 90% parasite infection in Rhodnius prolixus. The parasite behavior was investigated in vitro using fragments of the insect midgut. The addition of GIPLs in concentration as low as 50-100 nM impaired 95% the attachment of epimastigotes. Previous treatment of GIPLs with trifluoroacetic acid to remove the terminal beta-galactofuranosyl residues reversed 50% the epimastigote in vitro attachment. The binding sites of purified GIPLs on the luminal surface of the posterior midgut were exposed by immunofluorescence microscopy. These observations indicate that GIPLs are one of the components involved in the adhesion of T. cruzi to the luminal insect midgut surface and possibly one of the determinants of parasite infection in the insect vector.  相似文献   
223.
Paksoy N 《Acta cytologica》2007,51(2):222-226
BACKGROUND: Ectopic lesions are rarely encountered. Those that are derived from thyroid, breast, endometrium and salivary glands present with palpable masses that can mimic malignancy. Fine needle aspiration cytology (FNAC) is a practical procedure for the differential diagnosis of such lesions but can reveal surprising images for a cytopathologist. CASES: Three cases of discrete, ectopic lesions at different locations occurred. Case 1 was a 27-year-old woman. Upon diagnosis of a submandibular mass with a diameter of 1 cm, FNAC was performed. The smears showed crowded thyroid follicular cells comprising papillary clusters. A cytologic diagnosis of papillary thyroid lesion was rendered, Histopathology revealed that this lesion was ectopic thyroid tissue with focal chronic thyroiditis. Case 2 was a 38-year-old woman who presented with a painful mass with a diameter of 2.5 cm in the abdominal wall. The patient had undergone cesarean section 3 years earlier. The case was diagnosed on FNAC as low grade malignancy in which an adenocarcinoma/mesenchymal tumor distinction could not be made. The pathologic examination revealed endometriosis. Case 3 was a 31-year old woman who presented with a palpable nodule in the axillary region with a diameter of 1 cm. The patient had given birth 1 month earlier and was nursing. An FNAC diagnosis of lactation ectopic breast tissue was made. The mass disappeared by the end of lactation. CONCLUSION: FNAC of ectopic lesions may prove to be a diagnostic pitfall for cytopathologists. A cytopathologist who encounters a cellularpicturefrom a lesion that is outside the normal anatomic location must use a cautious diagnostic approach. Unless there are clear findings, the cytopathologist must refrain from a diagnosis of malignancy.  相似文献   
224.

Background

Metastatic tumor cells have acidic extracellular pH and differential electrochemical H+ gradients generated across their cell membranes by V-type H+-ATPases. This study shows that inhibition of the V-ATPases by the plant-derived monoterpene Myrtenal results in tumor cell death and decreased metastatic dissemination in mice.

Methods

The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model. Proton flux and extracellular acidification were directly evaluated at the surface of living cells using a non-invasive selective ion electrode approach.

Results

The inhibition of V-ATPases by 100?μM Myrtenal disrupted the electrochemical H+ gradient across the cell membranes, strongly induced cell death (4–5 fold), and decreased tumor cells migration and invasion in vitro. Myrtenal (15?mg/kg) also significantly reduced metastasis induced by B16F10 in vivo, further reinforcing that V-ATPase is a molecular target to halt the progression of cancers.

Conclusions

These data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H+ fluxes across the tumor cell membranes, disrupting pH signatures inherent in tumor progression, resulting in reprogrammed cell death and metastasis inhibition.

General significance

The work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related monoterpenes and derivatives as promising proton pump inhibitors with high chemotherapeutic potential.  相似文献   
225.
Akt/PKB is a central activator of multiple signaling pathways coupled with a large number of stimuli. Although both localization and activity of Akt in the nuclear compartment are well-documented, most Akt substrates identified so far are located in the cytoplasm, while nuclear substrates have remained elusive. A proteomic-based search for nuclear substrates of Akt was undertaken, exploiting 2D-electrophoresis/MS in combination with an anti-Akt phosphosubstrate antibody. This analysis indicated lamin A/C as a putative substrate of Akt in C2C12 cells. In vitro phosphorylation of endogenous lamin A/C by recombinant Akt further validated this result. Moreover, by phosphopeptide analysis and point mutation, we established that lamin A/C is phosphorylated by Akt at Ser404, in an evolutionary conserved Akt motif. To delve deeper into this, we raised an antibody against the lamin A Ser404 phosphopeptide which allowed us to determine that phosphorylation of lamin A Ser404 is triggered by the well-known Akt activator insulin, and is therefore to be regarded as a physiological response. Remarkably, expression of S404A lamin A in primary cells from healthy tissue caused the nuclear abnormalities that are a hallmark of Emery-Dreifuss muscular dystrophy (EDMD) cells. Indeed, it is known that mutations at several sites in lamin A/C cause autosomal dominant EDMD. Very importantly, we show here that Akt failed to phosphorylate lamin A/C in primary cells from an EDMD-2 patient with lamin A/C mutated in the Akt consensus motif. Together, our data demonstrate that lamin A/C is a novel signaling target of Akt, and implicate Akt phosphorylation of lamin A/C in the correct function of the nuclear lamina.  相似文献   
226.
Abstract 1 Host plant terpenes can influence attraction of conifer bark beetles to their aggregation pheromones: both synergistic and inhibitory compounds have been reported. However, we know little about how varying concentrations of individual monoterpenes affect responses. 2 We tested a gradient of ratios of α‐pinene, the predominant monoterpene in host pines in the Great Lakes region of North America, to Ips pini's pheromone, racemic ipsdienol plus lanierone. 3 Ips pini demonstrated a parabolic response, in which low concentrations of α‐pinene had no effect on attraction to its pheromone, intermediate concentrations were synergistic and high concentrations were inhibitory. These results suggest optimal release rates for population monitoring and suppression programmes. 4 Inhibition of bark beetle attraction to pheromones may be an important component of conifer defences. At terpene to pheromone ratios emulating emissions from trees actively responding to a first attack, arrival of flying beetles was low. This may constitute an additional defensive role of terpenes, which are also toxic to bark beetles at high concentrations. 5 Reduced attraction to a low ratio of α‐pinene to pheromone, as occurs when colonization densities become high and the tree's resin is largely depleted, might reflect a mechanism for preventing excessive crowding. 6 Thanasimus dubius, the predominant predator of I. pini, was also attracted to ipsdienol plus lanierone, but its response differed from that of its prey. Attraction increased across all concentrations of α‐pinene. This indicates that separate lures are needed to sample both predators and bark beetles effectively. It also provides an opportunity for maximizing pest removal while reducing adverse effects on beneficial species. This disparity further illustrates the complexity confronting natural enemies that track chemical signals to locate herbivores.  相似文献   
227.
228.
International Journal of Peptide Research and Therapeutics - Emergence of food borne pathogens and multidrug resistant organisms has enforced the screening of natural antimicrobial compounds....  相似文献   
229.
230.
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