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   1130篇
  免费   58篇
  1188篇
  2023年   5篇
  2022年   12篇
  2021年   26篇
  2020年   15篇
  2019年   21篇
  2018年   23篇
  2017年   32篇
  2016年   34篇
  2015年   47篇
  2014年   55篇
  2013年   73篇
  2012年   92篇
  2011年   91篇
  2010年   60篇
  2009年   60篇
  2008年   70篇
  2007年   72篇
  2006年   70篇
  2005年   46篇
  2004年   57篇
  2003年   48篇
  2002年   48篇
  2001年   7篇
  2000年   10篇
  1999年   12篇
  1998年   7篇
  1997年   9篇
  1996年   12篇
  1995年   7篇
  1994年   10篇
  1993年   6篇
  1992年   7篇
  1991年   4篇
  1990年   4篇
  1988年   2篇
  1987年   3篇
  1985年   1篇
  1984年   2篇
  1983年   2篇
  1982年   5篇
  1981年   2篇
  1979年   2篇
  1978年   2篇
  1977年   1篇
  1976年   3篇
  1975年   2篇
  1974年   3篇
  1973年   1篇
  1972年   1篇
  1971年   2篇
排序方式: 共有1188条查询结果,搜索用时 0 毫秒
1.
The purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol and/or Omega3 fatty acids. This approach was chosen in order to obtain at the same time two positive results: an enhanced drug permeation through nasal mucosa and a concomitant neuroprotective effect. Several liposome formulations were prepared using the Reverse Phase Evaporation technique followed by membrane filter extrusion. In particular, liposome capacity to enhance drug permeation was evaluated by means of membrane permeation and cellular uptake studies. Furthermore, liposome effect on neuronal viability and intracellular ROS production was evaluated as well as their cytoprotective effect against oxidative stress. All liposome formulations showed a mean diameter in the range of 175?nm to 219?nm with polydispersity index lower than 0.22, a lightly negative zeta potential and excellent encapsulation efficiency. Moreover, along with good mucoadhesive properties, multifunctional liposomes showed a markedly increase in tacrine permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of α-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes.  相似文献   
2.
Summary The pattern of DNA and RNA puffs in pair VII of polytene chromosomes has been investigated in the suspensor ofPhaseolus coccineus during early embryo development. The pattern of3H-TdR and3H-U incorporation has been also detected. Collected data indicate that: 1. both heterochromatic regions, p11 and q(111+112), of chromosome pair VII, organize large DNA puffs; 2. DNA puffs of both regions are specific of different embryo differentiation steps; 3. a seasonal influence on the DNA puffing seems also to be present, as demonstrated by the comparison of the results collected in two different crops; 4. the incorporation experiment by3H-TdR evidences that not all DNA puffs show clustered labeling; 5. the RNA puffing of the two regions seems also to be specific of determined embryo stages.  相似文献   
3.
The murine monoclonal antibody (Mab) MBr1, raised against thebreast cancer cell line MCF7, recognizes a saccharidic epitopeoverexpressed on a high percentage of human breast, ovary, andlung carcinomas. This antigen was originally identified on theimmunogen as a globo-series glycosphingolipid with an H-likedeterminant at its terminus (globo-H). We report here the biologicalcharacterization of the entire globo-H hexasaccharide and fivesynthetic oligosaccharides representing fragments of the entirestructure andlor different anomeric configurations. Using competitivebinding assays on live cells, we identified the residues andthe linkages essential for mimicry of the cellular antigensrecognized by Mab MBr1 on the breast carcinoma cell line MCF7and small cell lung cancer cell line POVD. The terminal tetrasaccharidicfragment of globo-H is the oligosaccharide that most resemblesthe MBr1-defined epitope both on glycolipids and on glycoproteins.This information will help in the rational design of a highlyspecific reagent for active specific immunotherapy of carcinomasoverexpressing the MBr1-defined antigen. CaMBr1 immunotherapy monoclonal antibody oligosaccharides tumor-associated antigen  相似文献   
4.
The frequency of sister chromatid exchanges (SCEs) in two cell lines of Drosophila melanogaster with different karyotypes (XX and XY) was determined, considering (1) the distribution of SCEs within each chromosome, with reference to eu- and heterochromatin and (2) the distribution of SCEs in different chromosomes. A comparison was made between chromosome pairs within each karyotype and between the two different karyotypes. The following results were obtained. The SCEs are not randomly distributed along chromosomes, since exchanges were never observed in heterochromatin. SCEs are more frequent in XY than in XX cells; moreover, in both cell types there exists a significantly higher frequency of SCEs in the X chromosome than in the autosomes. These findings are discussed in relation to chromosome aberrations and mitotic recombination.  相似文献   
5.
The armored catfish Hypostomus affinis is a widespread Loricariidae fish in the Lajes Reservoir (22 degrees 42'-22 degrees 50' S; 43 degrees 53'-44 degrees 05' W), the largest lentic environment in the Rio de Janeiro State, but little is known about their reproductive biology. One hundred and twenty five females, captured from January 1996 to December 1997, were used to assess ovarian development (29 were used to determine fecundity). The oocyte distribution by size-diameter classes revealed the occurrence of two modes suggesting an asynchronic development of the ovaries. The total fecundity ranged from 1235 to 4304, averaging 2374. An exponential relationship between fecundity and total length was determined, and a direct linear relationship was found between fecundity and total weight and gonad weight.  相似文献   
6.
Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites.Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets.In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia.In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected.In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties.  相似文献   
7.
In arid environments, direct facilitation (microhabitat amelioration) and indirect facilitation (‘associational resistance’ via protection from herbivory) among plants of different species may act simultaneously. Little is known about their relative effects. One way to disentangle the effects is by evaluating spatial associations. We examined the relative importance of these two mechanisms of facilitation in the semiarid Chaco vegetation of north‐central Argentina, through an eight‐way observational study in which we quantified the degree of spatial association between saplings of each of two key tree species, Schinopsis lorentzii (Anacardiaceae) and Aspidosperma quebracho‐blanco (Apocynaceae), with shrub neighbours either possessing spines or without spines and in both an ungrazed site and a site with a long history of cattle grazing. We analysed data across 400 subparcels at each site with spatial analysis by distance indices. Saplings of both tree species showed positive spatial associations with spiny shrubs in the grazed site but not in the ungrazed site, and never with non‐spiny shrubs. This result suggests that spiny shrubs may indeed provide associational resistance for saplings of key tree species in grazed habitats in these dry subtropical forests, that is, that indirect facilitation may predominate over direct facilitation. If confirmed by experimental studies, this result can have implications for the silvopastoral management of rapidly expanding ranches in the semiarid Chaco, where current practice includes the near elimination of native shrubs.  相似文献   
8.
It is generally assumed that the functional consequences of stimulation with Ca2+ -mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ "sensor" raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a "third messenger" via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+.  相似文献   
9.
Global interest in sugarcane has increased significantly in recent years due to its economic impact on sustainable energy production. Sugarcane breeding and better agronomic practices have contributed to a huge increase in sugarcane yield in the last 30?years. Additional increases in sugarcane yield are expected to result from the use of biotechnology tools in the near future. Genetically modified (GM) sugarcane that incorporates genes to increase resistance to biotic and abiotic stresses could play a major role in achieving this goal. However, to bring GM sugarcane to the market, it is necessary to follow a regulatory process that will evaluate the environmental and health impacts of this crop. The regulatory review process is usually accomplished through a comparison of the biology and composition of the GM cultivar and a non-GM counterpart. This review intends to provide information on non-GM sugarcane biology, genetics, breeding, agronomic management, processing, products and byproducts, as well as the current technologies used to develop GM sugarcane, with the aim of assisting regulators in the decision-making process regarding the commercial release of GM sugarcane cultivars.  相似文献   
10.
The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine.  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