全文获取类型
收费全文 | 470篇 |
免费 | 17篇 |
专业分类
487篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 16篇 |
2015年 | 26篇 |
2014年 | 38篇 |
2013年 | 14篇 |
2012年 | 40篇 |
2011年 | 33篇 |
2010年 | 28篇 |
2009年 | 24篇 |
2008年 | 20篇 |
2007年 | 35篇 |
2006年 | 32篇 |
2005年 | 24篇 |
2004年 | 20篇 |
2003年 | 31篇 |
2002年 | 22篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1984年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有487条查询结果,搜索用时 0 毫秒
1.
2.
Karine Salin Sonya K. Auer Agata M. Rudolf Graeme J. Anderson Andrew G. Cairns William Mullen Richard C. Hartley Colin Selman Neil B. Metcalfe 《Biology letters》2015,11(9)
There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. 相似文献
3.
Mohamed?F?Mitwally Sonya?Abdel-Razeq Robert?F?CasperEmail author 《Reproductive biology and endocrinology : RB&E》2004,2(1):55
Background
There are different factors that influence treatment outcome after ovarian stimulation and timed-intercourse or intrauterine insemination (IUI). After patient age, it has been suggested that timing of insemination in relation to ovulation is probably the most important variable affecting the success of treatment. The objective of this study is to study the value of human chorionic gonadotropin (hCG) administration and occurrence of luteinizing hormone (LH) surge in timing insemination on the treatment outcome after follicular monitoring with timed-intercourse or intrauterine insemination, with or without ovarian stimulation. 相似文献4.
5.
Sebastian R. Freeman Xueting Jin Joshua J. Anzinger Qing Xu Sonya Purushothaman Michael B. Fessler Lia Addadi Howard S. Kruth 《Journal of lipid research》2014,55(1):115-127
Previous studies have demonstrated that the ATP-binding cassette transporters (ABC)A1 and ABCG1 function in many aspects of cholesterol efflux from macrophages. In this current study, we continued our investigation of extracellular cholesterol microdomains that form during enrichment of macrophages with cholesterol. Human monocyte-derived macrophages and mouse bone marrow-derived macrophages, differentiated with macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulation factor (GM-CSF), were incubated with acetylated LDL (AcLDL) to allow for cholesterol enrichment and processing. We utilized an anti-cholesterol microdomain monoclonal antibody to reveal pools of unesterified cholesterol, which were found both in the extracellular matrix and associated with the cell surface, that we show function in reverse cholesterol transport. Coincubation of AcLDL with 50 μg/ml apoA-I eliminated all extracellular and cell surface-associated cholesterol microdomains, while coincubation with the same concentration of HDL only removed extracellular matrix-associated cholesterol microdomains. Only at an HDL concentration of 200 µg/ml did HDL eliminate the cholesterol microdomains that were cell-surface associated. The deposition of cholesterol microdomains was inhibited by probucol, but it was increased by the liver X receptor (LXR) agonist TO901317, which upregulates ABCA1 and ABCG1. Extracellular cholesterol microdomains did not develop when ABCG1-deficient mouse bone marrow-derived macrophages were enriched with cholesterol. Our findings show that generation of extracellular cholesterol microdomains is mediated by ABCG1 and that reverse cholesterol transport occurs not only at the cell surface but also within the extracellular space. 相似文献
6.
A microarray has been designed using 62,358 probes matched to both prokaryotic and eukaryotic small-subunit ribosomal RNA genes. The array categorized environmental DNA to specific phylogenetic clusters in under 9 h. To a background of DNA generated from natural outdoor aerosols, known quantities of rRNA gene copies from distinct organisms were added producing corresponding hybridization intensity scores that correlated well with their concentrations (r=0.917). Reproducible differences in microbial community composition were observed by altering the genomic DNA extraction method. Notably, gentle extractions produced peak intensities for Mycoplasmatales and Burkholderiales, whereas a vigorous disruption produced peak intensities for Vibrionales, Clostridiales, and Bacillales. 相似文献
7.
Faber SC Robinson ML Makarenkova HP Lang RA 《Development (Cambridge, England)》2002,129(15):3727-3737
We have investigated the role of Bmp signaling in development of the mouse lens using three experimental strategies. First, we have shown that the Bmp ligand inhibitor noggin can suppress the differentiation of primary lens fiber cells in explant culture. Second, we have expressed a dominant-negative form of the type 1 Bmp family receptor Alk6 (Bmpr1b -- Mouse Genome Informatics) in the lens in transgenic mice and shown that an inhibition of primary fiber cell differentiation can be detected at E13.5. Interestingly, the observed inhibition of primary fiber cell development was asymmetrical and appeared only on the nasal side of the lens in the ventral half. Expression of the inhibitory form of Alk6 was driven either by the alpha A-cystallin promoter or the ectoderm enhancer from the Pax6 gene in two different transgenes. These expression units drive transgene expression in distinct patterns that overlap in the equatorial cells of the lens vesicle at E12.5. Despite the distinctions between the transgenes, they caused primary fiber cell differentiation defects that were essentially identical, which implied that the equatorial lens vesicle cells were responding to Bmp signals in permitting primary fiber cells to develop. Importantly, E12.5 equatorial lens vesicle cells showed cell-surface immunoreactivity for bone-morphogenetic protein receptor type 2 and nuclear immunoreactivity for the active, phosphorylated form of the Bmp responsive Smads. This indicated that these cells had the machinery for Bmp signaling and were responding to Bmp signals. We conclude that Bmp signaling is required for primary lens fiber cell differentiation and, given the asymmetry of the differentiation inhibition, that distinct differentiation stimuli may be active in different quadrants of the eye. 相似文献
8.
Marie‐Josée Demers Sonya Thibodeau Dominique Noël Naoya Fujita Takashi Tsuruo Rémy Gauthier Mélina Arguin Pierre H. Vachon 《Journal of cellular biochemistry》2009,107(4):639-654
Herein, we investigated the survival roles of Fak, Src, MEK/Erk, and PI3‐K/Akt‐1 in intestinal epithelial cancer cells (HCT116, HT29, and T84), in comparison to undifferentiated and differentiated intestinal epithelial cells (IECs). We report that: (1) cancer cells display striking anoikis resistance, as opposed to undifferentiated/differentiated IECs; (2) under anoikis conditions and consequent Fak down‐activation, cancer cells nevertheless exhibit sustained Fak–Src interactions and Src/MEK/Erk activation, unlike undifferentiated/differentiated IECs; however, HCT116 and HT29 cells exhibit a PI3‐K/Akt‐1 down‐activation, as undifferentiated/differentiated IECs, whereas T84 cells do not; (3) cancer cells require MEK/Erk for survival, as differentiated (but not undifferentiated) IECs; however, T84 cells do not require Fak and HCT116 cells do not require PI3‐K/Akt‐1, in contrast to the other cells studied; (4) Src acts as a cornerstone in Fak‐mediated signaling to MEK/Erk and PI3‐K/Akt‐1 in T84 cells, as in undifferentiated IECs, whereas PI3‐K/Akt‐1 is Src‐independent in HCT116, HT29 cells, as in differentiated IECs; and (5) EGFR activity inhibition abrogates anoikis resistance in cancer cells through a loss of Fak–Src interactions and down‐activation of Src/MEK/Erk (T84, HCT116, HT29 cells) and PI3‐K/Akt‐1 (T84 cells). Hence, despite distinctions in signaling behavior not necessarily related to undifferentiated or differentiated IECs, intestinal epithelial cancer cells commonly display an EGFR‐mediated sustained activation of Src under anoikis conditions. Furthermore, such sustained Src activation confers anoikis resistance at least in part through a consequent sustenance of Fak–Src interactions and MEK/Erk activation, thus not only overriding Fak‐mediated signaling to MEK/Erk and/or PI3‐K/Akt‐1, but also the requirement of Fak and/or PI3‐K/Akt‐1 for survival. J. Cell. Biochem. 107: 639–654, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
9.
Taraban VY Martin S Attfield KE Glennie MJ Elliott T Elewaut D Van Calenbergh S Linclau B Al-Shamkhani A 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4615-4620
Activation of invariant NK T (iNKT) cells with the glycolipid alpha-galactosylceramide promotes CD8(+) cytotoxic T cell responses, a property that has been used to enhance the efficacy of antitumor vaccines. Using chimeric mice, we now show that the adjuvant properties of iNKT cells require that CD40 triggering and Ag presentation to CD8(+) T cells occur on the same APCs. We demonstrate that injection of alpha-galactosylceramide triggers CD70 expression on splenic T cell zone dendritic cells and that this is dependent on CD40 signaling. Importantly, we show that blocking the interaction between CD70 and CD27, its costimulatory receptor on T cells, abrogates the ability of iNKT cells to promote a CD8(+) T cell response and abolishes the efficacy of alpha-GalCer as an adjuvant for antitumor vaccines. These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8(+) T cells. 相似文献
10.
- Following the discovery of polyphagous shot hole borer Euwallacea fornicatus (Eichhoff) in Western Australia in September 2021, we estimated the likely economic damage that will result in the coming decades and the return on investment in eradication.
- A bioeconomic model was used to simulate the insect's spread and economic impact based on additional urban and commercial tree management costs. Two scenarios were examined, one in which an eradication policy response was initiated, and one in which it was not.
- With no eradication response, results indicated that median costs would reach A$6.8 million per annum in 30 years, with 98% of these costs relating to management in urban forests.
- We conclude that the eradication funding currently proposed, involving an investment of A$45.0 million over 3 years, will not generate sufficient benefits to offset costs in the short-term, but may produce net benefits in the longer term.