全文获取类型
收费全文 | 3117篇 |
免费 | 207篇 |
专业分类
3324篇 |
出版年
2024年 | 4篇 |
2023年 | 28篇 |
2022年 | 48篇 |
2021年 | 94篇 |
2020年 | 59篇 |
2019年 | 73篇 |
2018年 | 96篇 |
2017年 | 90篇 |
2016年 | 121篇 |
2015年 | 211篇 |
2014年 | 206篇 |
2013年 | 264篇 |
2012年 | 309篇 |
2011年 | 295篇 |
2010年 | 189篇 |
2009年 | 158篇 |
2008年 | 194篇 |
2007年 | 168篇 |
2006年 | 146篇 |
2005年 | 131篇 |
2004年 | 119篇 |
2003年 | 87篇 |
2002年 | 57篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 18篇 |
1998年 | 18篇 |
1997年 | 16篇 |
1996年 | 9篇 |
1995年 | 3篇 |
1994年 | 12篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1969年 | 2篇 |
1956年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有3324条查询结果,搜索用时 0 毫秒
51.
Cláudia Marques Diana Teixeira Ana Cunha Manuela Meireles Diogo Pestana Elisa Keating Conceição Calhau Rosário Monteiro Ana Faria 《Cell biology and toxicology》2013,29(4):293-302
Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and 3H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. 3H-Deoxyglucose (3H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and 3H-thymidine incorporation (P?<?0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal 3H-DG uptake by adipocytes (P?<?0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of 3H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX. 相似文献
52.
Sonia Eligini Mauro Crisci Elisa Bono Paola Songia Elena Tremoli Gualtiero I. Colombo Susanna Colli 《Journal of cellular physiology》2013,228(7):1464-1472
Tissue macrophages are resident phagocytes that acquire specific phenotypes according to the microenvironment. Morphological and functional heterogeneity has been evidenced in different homeostatic and pathological conditions. Indeed, the nature of macrophage subsets may have either harmful or beneficial functions in disease progression/resolution. Therefore the possibility to pharmacologically manipulate heterogeneity represents a relevant challenge. Since human tissue macrophages are not easily obtained, various in vitro models are currently used that do not adequately reflect the heterogeneity and plasticity of tissue macrophages. We had previously reported that two dominant and distinct macrophage morphotypes co‐exist in the same culture of human monocytes spontaneously differentiated for 7 days in autologous serum. The present study was aimed to the phenotypic characterization of these morphotypes, that is, round‐ and spindle‐shaped. We observed that, besides substantial differences in cytoskeleton architecture, round monocyte‐derived macrophages (MDMs) showed higher lipid content, increased macropinocytosis/efferocytosis capacity, and overexpression of CD163, interleukin (IL)‐10, and transforming growth factor (TGF) β2. Conversely, spindle MDMs exhibited enhanced respiratory burst and higher expression of the chemokine (C‐C motif) ligands 18 and 24 (CCL18 and CCL24). Overall, round MDMs show functional traits reminiscent of the non‐inflammatory and reparative M2 phenotype, whereas spindle MDMs exhibit a pro‐inflammatory profile and express genes driving lymphocyte activation and eosinophil recruitment. MDMs obtained in the culture condition herein described represent a valuable model to disentangle and manipulate the functional heterogeneity of tissue macrophages that has been disclosed in scenarios spanning from inflammatory and wounding responses to atherosclerotic lesions. J. Cell. Physiol. 228: 1464–1472, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
53.
54.
55.
56.
Elisa Tran Annabelle Chow Takeshi Goda Amy Wong Kim Blakely Michelle Rocha Samira Taeb Van C. Hoang Stanley K. Liu Urban Emmenegger 《Biochemical and biophysical research communications》2013
ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4BC74Ain vitro and in vivo, we show that the effects of ATG4BC74A are cell type, treatment, and context-dependent. ATG4BC74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response. 相似文献
57.
58.
Roberta Battistini Elisa Marcucci Marco Verani Graziano Di Giuseppe Fernando Dini Annalaura Carducci 《European journal of protistology》2013,49(3):381-388
The aim of the present work was to study the dynamics of the interactions between human adenovirus and ciliates under both experimental and field conditions. Experimental co-cultures of the ciliated protozoan Euplotes octocarinatus and human adenovirus (HAdV) type 2 were established and virus internalization was investigated using nested PCR and direct immunofluorescence (IF). In addition, to study protozoa-virus interactions in the field, wild ciliates were isolated from active sludges of a wastewater treatment plant and analyzed for the presence of adenovirus using direct IF. In vitro experiments revealed HAdV type 2 inside Euplotes cells after 15 min of contact and its persistence until at least 35 days post infection. In addition, our results showed the adsorption of adenovirus on the surface of wild ciliates. We conclude that HAdV is taken up by ciliates, however more studies are necessary in order to better investigate the mechanisms, the infectivity of internalized virus and the protective effects of internalization against disinfection. 相似文献
59.
Marzia Scortegagna Chelsea Ruller Surya K. De Elisa Barile Stan Krajewski Pedro Aza‐Blanc Roy Williams Anthony B. Pinkerton Michael Jackson Lynda Chin Maurizio Pellecchia Marcus Bosenberg Ze'ev A. Ronai 《Pigment cell & melanoma research》2013,26(1):136-142
To date, there are no effective therapies for tumors bearing NRAS mutations, which are present in 15–20% of human melanomas. Here we extend our earlier studies where we demonstrated that the small molecule BI‐69A11 inhibits the growth of melanoma cell lines. Gene expression analysis revealed the induction of interferon‐ and cell death‐related genes that were associated with responsiveness of melanoma cell lines to BI‐69A11. Strikingly, the administration of BI‐69A11 inhibited melanoma development in genetically modified mice bearing an inducible form of activated Nras and a deletion of the Ink4a gene (Nras(Q61K)::Ink4a?/?). Biweekly administration of BI‐69A11 starting at 10 weeks or as late as 24 weeks after the induction of mutant Nras expression inhibited melanoma development (100 and 36%, respectively). BI‐69A11 treatment did not inhibit the development of histiocytic sarcomas, which constitute about 50% of the tumors in this model. BI‐69A11‐resistant Nras(Q61K)::Ink4a?/? tumors exhibited increased CD45 expression, reflective of immune cell infiltration and upregulation of gene networks associated with the cytoskeleton, DNA damage response, and small molecule transport. The ability to attenuate the development of NRAS mutant melanomas supports further development of BI‐69A11 for clinical assessment. 相似文献
60.
Patricio H. Manríquez María Elisa Jara María Loreto Mardones Jorge M. Navarro Rodrigo Torres Marcos A. Lardies Cristian A. Vargas Cristian Duarte Stephen Widdicombe Joseph Salisbury Nelson A. Lagos 《PloS one》2013,8(7)