全文获取类型
收费全文 | 1449篇 |
免费 | 107篇 |
出版年
2024年 | 3篇 |
2023年 | 12篇 |
2022年 | 34篇 |
2021年 | 67篇 |
2020年 | 32篇 |
2019年 | 44篇 |
2018年 | 58篇 |
2017年 | 45篇 |
2016年 | 60篇 |
2015年 | 92篇 |
2014年 | 85篇 |
2013年 | 100篇 |
2012年 | 143篇 |
2011年 | 131篇 |
2010年 | 61篇 |
2009年 | 71篇 |
2008年 | 80篇 |
2007年 | 76篇 |
2006年 | 62篇 |
2005年 | 70篇 |
2004年 | 65篇 |
2003年 | 33篇 |
2002年 | 41篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 9篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1556条查询结果,搜索用时 562 毫秒
901.
Alejandra Idan Valencia-Cruz Laura I. Uribe-Figueroa Rodrigo Galindo-Murillo Karol Baca-López Anllely G. Gutiérrez Adriana Vázquez-Aguirre Lena Ruiz-Azuara Enrique Hernández-Lemus Carmen Mejía 《PloS one》2013,8(1)
Copper-based chemotherapeutic compounds Casiopeínas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis–in a process mediated by reactive oxygen species–for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions before establishing settings and parameters needed for their wide clinical application. In order to shorten the gap in this respect, we present a model proposal centered in the role played by intrinsic (or mitochondrial) apoptosis triggered by oxidative stress caused by the chemotherapeutic agent. This model has been inferred based on genome wide expression profiling in cervix cancer (HeLa) cells, as well as statistical and computational tests, validated via functional experiments (both in the same HeLa cells and also in a Neuroblastoma model, the CHP-212 cell line) and assessed by means of data mining studies. 相似文献
902.
Ramos Patricio Guajardo Joselin Moya-León María Alejandra Herrera Raúl 《Tree Genetics & Genomes》2016,12(3):1-12
Tree Genetics & Genomes - Gibberellins (GAs) have been widely used for many years to induce seedless grapevine and increase fruit set in production. However, the role of GAs and how they... 相似文献
903.
Praveen Govender Freddy Romero Dilip Shah Jesus Paez Shi-Ying Ding Libin Liu Adam Gower Elizabeth Baez Sherif Shawky Aly Paul Pilch Ross Summer 《PloS one》2013,8(4)
Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung architecture were associated with hypercellularity and the accumulation of lung macrophages. The increases in lung macrophages occurred without changes to circulating numbers of mononuclear cells and without evidence for increased proliferation. However, the increases in lung macrophages were associated with higher levels of macrophage chemotactic factors CXCL2 and CCL2 in BAL fluid from Cavin1−/− mice suggesting a possible mechanism by which these cells accumulate. In addition, lung macrophages from Cavin1−/− mice were larger and displayed measurable differences in gene expression when compared to macrophages from wild-type mice. Interestingly, macrophages were also increased in adipose tissue but not in liver, kidney or skeletal muscle from Cavin1−/− mice, and similar tissue specificity for macrophage accumulation was observed in lungs and adipose tissue from Caveolin1−/− mice. In conclusion, this study demonstrates an important role for Cavin1 in lung homeostasis and suggests that caveolae structural proteins are necessary for regulating macrophage number and phenotype in the lung. 相似文献
904.
905.
906.
Mauricio Baez Ricardo Cabrera Humberto?M. Pereira Alejandro Blanco Pablo Villalobos César?A. Ramírez-Sarmiento Andrés Caniuguir Victoria Guixé Richard?C. Garratt Jorge Babul 《Biophysical journal》2013,104(1):185-195
The enzymatic activity of secreted phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes is associated with bacterial virulence. Although the PI-PLC active site has no obvious lid, molecular-dynamics simulations suggest that correlated loop motions may limit access to the active site, and two Pro residues, Pro245 and Pro254, are associated with these correlated motions. Whereas the region containing both Pro residues is quite variable among PI-PLCs, it shows high conservation in virulence-associated, secreted PI-PLCs that bind to the surface of cells. These regions of the protein are also associated with phosphatidylcholine binding, which enhances PI-PLC activity. In silico mutagenesis of Pro245 disrupts correlated motions between the two halves of Bacillus thuringiensis PI-PLC, and Pro245 variants show significantly reduced enzymatic activity in all assay systems. PC still enhanced activity, but not to the level of wild-type enzyme. Mutagenesis of Pro254 appears to stiffen the PI-PLC structure, but experimental mutations had minor effects on activity and membrane binding. With the exception of P245Y, reduced activity was not associated with reduced membrane affinity. This combination of simulations and experiments suggests that correlated motions between the two halves of PI-PLC may be more important for enzymatic activity than for vesicle binding. 相似文献
907.
908.
909.
Ricardo V. García-Mayor Alejandra Larrañaga Vidal Maria F. Docet Caamaño Anunciación Lafuente Giménez 《Endocrinología y nutrición》2012,59(4):261-267
Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans. 相似文献
910.
Mercedes Romero Fernando Messina Roxana Depardo Emmanuel Marín Alicia Arechavala Nicolás Lista Alejandra Rodríguez Gabriela Santiso 《Revista iberoamericana de micología》2021,38(1):23-26
A 31-year-old woman, with signs of HIV infection (oral thrush, weight loss, asthenia) presented to our hospital with dyspnea and fever. A rapid HIV test yielded a positive result, and cryptococcal capsular antigen was detected in serum. In the mycological study of the clinical respiratory samples, yeasts compatible with Cryptococcus were observed under light microscope in a wet mount; structures compatible with Pneumocystis jirovecii were also observed in Giemsa stain. Treatment for both pathologies was prescribed but, unfortunately, the patient died 7 days after. The finding of two etiologic agents in the same clinical picture is rare but not exceptional, and it always must be considered in immunocompromised hosts. 相似文献