全文获取类型
收费全文 | 158篇 |
免费 | 11篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 7篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 18篇 |
2011年 | 12篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 16篇 |
2007年 | 10篇 |
2006年 | 7篇 |
2005年 | 2篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 7篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1993年 | 2篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有169条查询结果,搜索用时 437 毫秒
101.
Luisa Lorenzi Giovanna Tabellini William Vermi Daniele Moratto Fulvio Porta Lucia D. Notarangelo Ornella Patrizi Silvano Sozzani Genevieve de Saint Basile Sylvain Latour David Pace Silvia Lonardi Fabio Facchetti Raffaele Badolato Silvia Parolini 《PloS one》2013,8(11)
Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56brightCD16− Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients. 相似文献
102.
103.
104.
Francesco Esposito Marco De Martino Floriana Forzati 《Cell cycle (Georgetown, Tex.)》2014,13(23):3636-3639
Two pseudogenes for HMGA1, whose overexpression has a critical role in cancer progression, have been identified. They act as decoy for miRNAs that are able to target the HMGA1 gene then enhancing cell proliferation and migration. Moreover, these pseudogenes contain sequences that are potential target sites for cancer-related miRNAs. Interestingly, HMGA1 pseudogenes are highly expressed in human anaplastic thyroid carcinomas, that is one of the most aggressive tumor in mankind, but almost undetectable in well differentiated thyroid carcinomas. 相似文献
105.
Fiorentini S Marconi P Avolio M Marini E Garrafa E Caracciolo S Rossi D Bozac A Becker PD Gentili F Facchetti F Guzman CA Manservigi R Caruso A 《Microbes and infection / Institut Pasteur》2007,9(8):988-996
Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses. 相似文献
106.
107.
Lopez J John SW Tenev T Rautureau GJ Hinds MG Francalanci F Wilson R Broemer M Santoro MM Day CL Meier P 《Molecular cell》2011,42(5):569-583
E3 ligases mediate the covalent attachment of ubiquitin to target proteins thereby enabling ubiquitin-dependent signaling. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Cellular inhibitor of apoptosis (cIAP) proteins are E3 ligases that modulate diverse biological processes such as cell survival, proliferation, and migration. Here, we have solved the structure of the caspase recruitment domain (CARD) of cIAP1 and identified that it is required for cIAP1 autoregulation. We demonstrate that the CARD inhibits activation of cIAP1's E3 activity by preventing RING dimerization, E2 binding, and E2 activation. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Further, CARD-mediated autoregulation is also necessary to maximally suppress caspase-8-dependent apoptosis and vascular tree degeneration in vivo. Taken together, our data reveal mechanisms by which the E3 ligase activity of cIAP1 is controlled, and how its deregulation impacts on cell proliferation, migration and cell survival. 相似文献
108.
Stevenson MM Ing R Berretta F Miu J 《International journal of biological sciences》2011,7(9):1311-1322
Although a clearer understanding of the underlying mechanisms involved in protection and immunopathology during blood-stage malaria has emerged, the mechanisms involved in regulating the adaptive immune response especially those required to maintain a balance between beneficial and deleterious responses remain unclear. Recent evidence suggests the importance of CD11c+ dendritic cells (DC) and CD4+Foxp3+ regulatory T cells in regulating immune responses during infection and autoimmune disease, but information concerning the contribution of these cells to regulating immunity to malaria is limited. Here, we review recent findings from our laboratory and others in experimental models of malaria in mice and in Plasmodium-infected humans on the roles of DC and natural regulatory T cells in regulating adaptive immunity to blood-stage malaria. 相似文献
109.
Cea M Soncini D Fruscione F Raffaghello L Garuti A Emionite L Moran E Magnone M Zoppoli G Reverberi D Caffa I Salis A Cagnetta A Bergamaschi M Casciaro S Pierri I Damonte G Ansaldi F Gobbi M Pistoia V Ballestrero A Patrone F Bruzzone S Nencioni A 《PloS one》2011,6(7):e22739
Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD(+)-independent HDACs are an established therapeutic target, the relevance of NAD(+)-dependent HDACs (sirtuins) in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+)-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527) and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+) levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+)-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited. 相似文献
110.
A trinuclear copper(II) complex, [Cu3(2,5-pydc)2(Me5dien)2(BF4)2(H2O)2] · H2O 1, has been constructed from 2,5-pyridine-dicarboxylato bridges (2,5-pydc2−) and N,N,N′,N″,N″-pentamethyl-diethylenetriamine (Me5dien) acting as a blocking ligand. The copper ions, within the centrosymmetric trinuclear cations, are connected by two 2,5-pydc2− bridges, with an intramolecular Cu···Cu separation of 8.432 Å. The central copper ion exhibits an elongated octahedral geometry, with semicoordinated ions, while the terminal ones are pentacoordinated (distorted square-pyramidal geometry). The cryomagnetic investigation of 1 reveals an antiferromagnetic coupling of the copper(II) ions (J = −5.9 cm−1, H = −JSCu1SCu2 − JSCu2SCu1a). 相似文献