全文获取类型
收费全文 | 410篇 |
免费 | 37篇 |
出版年
2023年 | 4篇 |
2022年 | 5篇 |
2021年 | 12篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 20篇 |
2015年 | 19篇 |
2014年 | 17篇 |
2013年 | 31篇 |
2012年 | 36篇 |
2011年 | 31篇 |
2010年 | 22篇 |
2009年 | 14篇 |
2008年 | 31篇 |
2007年 | 30篇 |
2006年 | 27篇 |
2005年 | 18篇 |
2004年 | 23篇 |
2003年 | 17篇 |
2002年 | 19篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有447条查询结果,搜索用时 15 毫秒
101.
102.
Mariana Melchiorre Germán Robert Victorio Trippi Roberto Racca H. Ramiro Lascano 《Plant Growth Regulation》2009,57(1):57-68
In previous works, we have established a correlation between antioxidant system response and tolerance to drought, osmotic
stress and photooxidative stress of different wheat cultivars with contrasting drought tolerance. In the present work, a protocol
to obtain and transform wheat protoplasts was established. Transgenic protoplasts with Manganese Superoxide Dismutase (Mn-SOD)
(E.C.: 1.15.1.1) and Glutathione Reductase (GR) (E.C.: 1.6.4.2) overexpression in chloroplasts were obtained, and their responses
to photooxidative stress were characterized. Protoplasts with Mn-SOD or GR overexpression, showed different responses and
tolerance to photooxidative stress. Protoplasts with Mn-SOD overexpression showed lower levels of oxidative damage, higher
level of endogenous hydrogen peroxide and a great induction of total SOD and GR activities during photooxidative treatments.
In protoplasts with GR overexpression the oxidative damage provoked by the photooxidative treatment was similar to control
protoplasts, the GSH content and GSH/GSH + GSSG ratio were higher than control and Mn-SOD transformed protoplast, and total
SOD and GR activities were not induced. Our results suggest that the differential responses and tolerance to photooxidative
stress given by Mn-SOD or GR overexpression, also depend on the effects of these enzyme activities over the cellular redox
state balance, which modulate the responses to photooxidative stress. 相似文献
103.
Marta Moya M. José Gómez-Lechón José V. Castell Ramiro Jover 《Chemico-biological interactions》2010,184(3):376-387
Steatosis is the first step in the development of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms involved in its pathogenesis are not fully understood. Many nuclear receptors (NRs) involved in energy homeostasis and biotransformation constitute a network connecting fatty acids, cholesterol and xenobiotic metabolisms; therefore, multiple NRs and their ligands may play a prominent role in liver fat metabolism and accumulation. In this study we have attempted to gain insight into the relevance of the NR superfamily in NAFLD by investigating the steatogenic potential of 76 different NR ligands in fatty acid overloaded human hepatocytes and hepatoma cells. Moreover, we have determined the mRNA expression level of 24 NRs to correlate the steatogenic potential of the ligands with the expression of their associated NRs in the cultured cells. Our results demonstrate that 18% of the examined NR ligands enhanced lipid accumulation in human hepatocytes and/or hepatoma cells. Among them, ligands of PPARγ (e.g., thiazolidinediones), LXR (paxilline and 24(S),25-epoxycholesterol), PXR (hyperforin), CAR (3α,5α-androstenol), ERα (tamoxifen), FXR (Z-guggulsterone), VDR (25-hydroxyvitamin D3) and particular retinoids and farnesoids showed a significant pro-steatotic effect. The mRNA level of most of the NRs examined was well preserved in human hepatocytes, but HepG2 showed a deranged profile, where many of the receptors had a marginal or negligible level of expression in comparison with the human liver. By comparing the steatogenic effect of NR ligands with the NR expression levels, we conclude that LXR, PXR, RAR and PPARγ ligands likely induce fat accumulation by a NR-dependent mechanism. Indeed, over-expression of PXR in HepG2 cells enhanced the steatogenic effect of hyperforin and rifampicin. However, the accumulation of fat induced by other ligands did not correlate with the expression of their associated NR. Our results also suggest that human hepatocytes cultured with free fatty acids offer a highly valuable in vitro system to investigate the pathogenesis and therapeutics of the human fatty liver. 相似文献
104.
Gangliosides are sialic acid-containing glycosphingolipids present on mammalian plasma membranes, where they participate in cell-surface events such as modulation of growth factor receptors and cell-to-cell and cell-to-matrix interactions. Antibodies to gangliosides have been associated with a wide range of clinically identifiable acute and chronic neuropathy syndromes. In addition, antibodies to tumor-associated gangliosides are being used as therapeutic agents. Their binding to and release from cell membranes and intracellular destinations have not so far been extensively examined. In this study, we characterized in both GD3 ganglioside-expressing Chinese hamster ovary (CHO)-K1 and SK-Mel 28 melanoma cells the intracellular trafficking and subcellular localization of the mouse monoclonal antibody to GD3, R24. By biochemical techniques and detailed confocal microscopic analysis, we demonstrate that the GD3-R24 antibody complex is rapidly and specifically internalized by a dynamin 2-independent pathway and then accumulates in the endocytic recycling compartment. In addition, we show that the R24 antibody exits the recycling compartment en route to the plasma membrane by a dynamin 2-dependent pathway sensitive to brefeldin A and monensin. Taken together, our results indicate that the GD3-R24 complex is endocytosed in GD3-expressing cells, accumulates in the recycling endosome, and is transported back to the plasma membrane via a route that involves clathrin-coated vesicles. 相似文献
105.
MicroRNA expression and function in cancer 总被引:9,自引:0,他引:9
MicroRNAs are small non-coding RNAs of 19-24 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent work supports a role for miRNAs in the initiation and progression of human malignancies. Large high-throughput studies in patients revealed that miRNA profiling have the potential to classify tumors with high accuracy and predict outcome. Functional studies, some of which involve animal models, indicate that miRNAs act as tumor suppressors and oncogenes. Here, we summarize miRNA-profiling studies in human malignancies and examine the role of miRNAs in the pathogenesis of cancer. We also discuss the implications of these findings for the diagnosis and treatment of cancer. 相似文献
106.
Alvarez V Rodríguez-Sáiz M de la Fuente JL Gudiña EJ Godio RP Martín JF Barredo JL 《Fungal genetics and biology : FG & B》2006,43(4):261-272
The conversion of beta-carotene into xanthophylls is a subject of great scientific and industrial interest. We cloned the crtS gene involved in astaxanthin biosynthesis from two astaxanthin producing strains of Xanthophyllomyces dendrorhous: VKPM Y2410, an astaxanthin overproducing strain, and the wild type ATCC 24203. In both cases, the ORF has a length of 3166 bp, including 17 introns, and codes for a protein of 62.6 kDa with similarity to cytochrome-P450 hydroxylases. crtS gene sequences from strains VKPM Y2410, ATCC 24203, ATCC 96594, and ATCC 96815 show several nucleotide changes, but none of them causes any amino acid substitution, except a G2268 insertion in the 13th exon of ATCC 96815 which causes a change in the reading frame. A G1470 --> A change in the 5' splicing region of intron 8 was also found in ATCC 96815. Both point mutations explain astaxanthin idiotrophy and beta-carotene accumulation in ATCC 96815. Mutants accumulating precursors of the astaxanthin biosynthetic pathway were selected from the parental strain VKPM Y2410 (red) showing different colors depending on the compound accumulated. Two of them were blocked in the biosynthesis of astaxanthin, M6 (orange; 1% astaxanthin, 71 times more beta-carotene) and M7 (orange; 1% astaxanthin, 58 times more beta-carotene, 135% canthaxanthin), whereas the rest produced lower levels of astaxanthin (5-66%) than the parental strain. When the crtS gene was expressed in M7, canthaxanthin accumulation disappeared and astaxanthin production was partially restored. Moreover, astaxanthin biosynthesis was restored when X. dendrorhous ATCC 96815 was transformed with the crtS gene. The crtS gene was heterologously expressed in Mucor circinelloides conferring to this fungus an improved capacity to synthesize beta-cryptoxanthin and zeaxanthin, two hydroxylated compounds from beta-carotene. These results show that the crtS gene is involved in the conversion of beta-carotene into xanthophylls, being potentially useful to engineer carotenoid pathways. 相似文献
107.
Lascano H. Ramiro; Gomez Leonardo D.; Casano Leonardo M.; Trippi Victorio S. 《Plant & cell physiology》1999,40(7):683-690
To study the mechanism of regulation of chloroplastic glutathionereductase (GR) under photooxidative conditions, GR activity,and the levels of NADPH, GSH and GSSG were measured in wheatchloroplasts under photooxidative light. GR was extremely labile,and the concentrations of GSH and GSSG progressively diminishedin chloroplasts prepared without ascorbate. The NADPH leveldid not significantly change during photooxidative treatment.The addition of 10 mM ascorbate to the incubation medium preventedthe decrease of GSH and GSSG and strongly protected GR activity.However, ascorbate had no effect on NADPH-dependent inhibitionof the chloroplastic GR purified from wheat leaves. We studiedthe effect of NADPH, temperature, pH and GSSG on the purifiedenzyme. The inhibition by NADPH was greatly dependent on temperatureand pH. NADPH inhibited GR by around 93% up to pH 7.5, but withina range of 8.0 to 9.5 the inhibition was only marginal. ThepH dependence of the NADPH inhibitory effect could be due, atleast in part, to different rates in the generation of NADPH-X,a derivative of NADPH which inactivates several pyridin nucleotidedehydrogenases. Furthermore, the NADPH-dependent inhibitionwas almost completely prevented by GSSG, but not by GSH. (Received July 9, 1998; Accepted April 30, 1999) 相似文献
108.
Redondo M Fragoso H Ortíz M Montero C Lona J Medellín JA Fría R Hernández V Franco R Machado H Rodríguez M de la Fuente J 《Experimental & applied acarology》1999,23(10):841-849
Throughout most of the twentieth century, tick infestations on cattle have been controlled with chemical acaricides, typically administered by dipping or spraying. This approach can cause environmental and residue problems and has created a high incidence of acaricide resistance within tick populations in the field. Recently we developed a vaccine against Boophilus microplus employing a recombinant Bm86 antigen preparation (Gavac), (Heber Biotec S.A., Havana, Cuba) which has been shown to induce a protective response in vaccinated animals. Here we show for the first time under field conditions a near 100% control of B. microplus populations resistant to pyrethroids and organophosphates, by an integrated system employing vaccination with Gavac and amidine treatments. This method effectively controls tick infestations while reducing the number of chemical acaricide treatments and consequently the rise of B. microplus populations resistant to chemical acaricides. 相似文献
109.
110.
Bourhim M Darnige L Legallais C Arvieux J Cevallos R Pouplard C Vijayalakshmi MA 《Journal of molecular recognition : JMR》2003,16(3):125-130
The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies associated with arterial and/or venous thrombosis, and recurrent abortion accompanied often by thrombocytopenia. These antibodies are heterogeneous and react against phospholipid-binding proteins such as beta2-glycoprotein I (beta2GPI) and prothrombin. The recognition of anti-beta2-glycoprotein I (anti-beta2GPI) by platelet factor 4-heparin complex (PF4-Hc) has been previously evoked and partially confirmed by the present inhibition studies. Further, the anti-beta2-glycoprotein I antibodies were purified from a patient with primary antiphospholipid syndrome using Affi-gel-10-beta2GPI immunoaffinity chromatography. The purified anti-beta2GPI IgM as well as patient serum equally recognized PF4-Hc in ELISA mode. In order to substantiate this data and to better understand we studied an animal model using mouse active immunization with the purified human anti-beta2GPI. The mice showed a significant decrease in their platelet count. In addition the ELISA responses of the immunized mice sera were positive against both beta2GPI and PF4-Hc, substantiating the double recognition. Despite many previous reported animal model studies, this is the first time we have shown the specific recognition of anti-beta2GPI antibodies by PF4-Hc, the results in the induced mice correlating the data observed with some patients. 相似文献