全文获取类型
收费全文 | 611篇 |
免费 | 60篇 |
国内免费 | 2篇 |
专业分类
673篇 |
出版年
2023年 | 4篇 |
2022年 | 13篇 |
2021年 | 24篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 16篇 |
2017年 | 14篇 |
2016年 | 22篇 |
2015年 | 44篇 |
2014年 | 23篇 |
2013年 | 35篇 |
2012年 | 60篇 |
2011年 | 40篇 |
2010年 | 35篇 |
2009年 | 26篇 |
2008年 | 34篇 |
2007年 | 47篇 |
2006年 | 21篇 |
2005年 | 31篇 |
2004年 | 26篇 |
2003年 | 22篇 |
2002年 | 20篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1992年 | 4篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1969年 | 3篇 |
1968年 | 3篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1961年 | 1篇 |
1873年 | 1篇 |
1857年 | 2篇 |
排序方式: 共有673条查询结果,搜索用时 0 毫秒
81.
82.
Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their proliferative response to mechanical strain in vitro. Primary osteoblast-like cells were derived from cortical bone of adult mice lacking functional Lrp5 (Lrp5(-/-)), those heterozygous for the human G171V High Bone Mass (HBM) mutation (LRP5(G171V)) and their WT littermates (WT(Lrp5), WT(HBM)). Osteoblast proliferation over time was significantly higher in cultures of cells from LRP5(G171V) mice compared to their WT(HBM) littermates, and lower in Lrp5(-/-) cells. Cells from female LRP5(G171V) mice grew more rapidly than those from males, whereas cells from female Lrp5(-/-) mice grew more slowly than those from males. Apoptosis induced by serum withdrawal was significantly higher in cultures from Lrp5(-/-) mice than in those from WT(HBM) or LRP5(G171V) mice. Exposure to a single short period of dynamic mechanical strain was associated with a significant increase in cell number but this response was unaffected by genotype which also did not change the 'threshold' at which cells responded to strain. In conclusion, the data presented here suggest that Lrp5 loss and gain of function mutations result in cell-autonomous alterations in osteoblast proliferation and apoptosis but do not alter the proliferative response of osteoblasts to mechanical strain in vitro. 相似文献
83.
AP Herbert M Riesen L Bloxam E Kosmidou BM Wareing JR Johnson MM Phelan SR Pennington LY Lian A Morgan 《PloS one》2012,7(7):e41975
Dietary restriction (DR) extends lifespan in yeast, worms, flies and mammals, suggesting that it may act via conserved processes. However, the downstream mechanisms by which DR increases lifespan remain unclear. We used a gel based proteomic strategy to identify proteins whose expression was induced by DR in yeast and thus may correlate with longevity. One protein up-regulated by DR was Hsp12, a small heat shock protein induced by various manipulations known to retard ageing. Lifespan extension by growth on 0.5% glucose (DR) was abolished in an hsp12Δ strain, indicating that Hsp12 is essential for the longevity effect of DR. In contrast, deletion of HSP12 had no effect on growth under DR conditions or a variety of environmental stresses, indicating that the effect of Hsp12 on lifespan is not due to increased general stress resistance. Unlike other small heat shock proteins, recombinant Hsp12 displayed negligible in vitro molecular chaperone activity, suggesting that its cellular function does not involve preventing protein aggregation. NMR analysis indicated that Hsp12 is monomeric and intrinsically unfolded in solution, but switches to a 4-helical conformation upon binding to membrane-mimetic SDS micelles. The structure of micelle-bound Hsp12 reported here is consistent with its recently proposed function as a membrane-stabilising 'lipid chaperone'. Taken together, our data suggest that DR-induced Hsp12 expression contributes to lifespan extension, possibly via membrane alterations. 相似文献
84.
Martin Gilbert David Bickford Leanne Clark Arlyne Johnson Priscilla H. Joyner Lucy Ogg Keatts Kongsy Khammavong Long Nguyễn Văn Alisa Newton Tiffany P. W. Seow Scott Roberton Soubanh Silithammavong Sinpakhone Singhalath Angela Yang Tracie A. Seimon 《EcoHealth》2012,9(4):386-398
Amphibian trade is known to facilitate the geographic spread of pathogens. Here we assess the health of amphibians traded in Southeast Asia for food or as pets, focusing on Batrachochytrium dendrobatidis (Bd), ranavirus and general clinical condition. Samples were collected from 2,389 individual animals at 51 sites in Lao PDR, Cambodia, Vietnam and Singapore for Bd screening, and 74 animals in Cambodia and Vietnam for ranavirus screening. Bd was found in one frog (n = 347) in Cambodia and 13 in Singapore (n = 419). No Bd was found in Lao PDR (n = 1,126) or Vietnam (n = 497), and no ranavirus was found in Cambodia (n = 70) or Vietnam (n = 4). Mild to severe dermatological lesions were observed in all East Asian bullfrogs Hoplobatrachus rugolosus (n = 497) sampled in farms in Vietnam. Histologic lesions consistent with sepsis were found within the lesions of three frogs and bacterial sepsis in two (n = 4); one had Gram-negative bacilli and one had acid-fast organisms consistent with mycobacterium sp. These results confirm that Bd is currently rare in amphibian trade in Southeast Asia. The presence of Mycobacterium-associated disease in farmed H. rugolosus is a cause for concern, as it may have public health implications and indicates the need for improved biosecurity in amphibian farming and trade. 相似文献
85.
Bloedon LT Dunbar R Duffy D Pinell-Salles P Norris R DeGroot BJ Movva R Navab M Fogelman AM Rader DJ 《Journal of lipid research》2008,49(6):1344-1352
Patients with coronary heart disease or equivalent risk received a single dose of 30, 100, 300, or 500 mg of unformulated D-4F (n = 8, each dose) or placebo (n = 8) under fasting conditions. An additional 10 patients received 500 mg (n = 8) or placebo (n = 2) with a low-fat meal. There were no significant trends in any safety parameter. D-4F was detectable in plasma at all doses with a T(max) of 30 min, 1 h, and 2 h for 30, 100, and > or = 300 mg, respectively. The area under the curve((0-t)) was 27.81 ng/hr/ml and 54.71 ng/hr/ml for the 300 mg and 500 mg dose groups, respectively, and 17.96 ng/hr/ml for the 500 mg dose given with food. HDL from each time point for each subject was tested for its ability to inhibit LDL-induced monocyte chemotactic activity in cultures of human aortic endothelial cells. The values obtained were normalized to 1.0 for LDL alone to obtain the HDL inflammatory index. This index significantly improved at 4 h at the 300 mg dose and at 2 h at the 500 mg dose compared with placebo (P < 0.05). There were no changes in plasma lipid or lipoprotein levels. We conclude that unformulated D-4F has low bioavailability that is improved under fasting conditions, and that a single dose of D-4F is safe and well tolerated and may improve the HDL anti-inflammatory index. 相似文献
86.
87.
Hansen U Zioupos P Simpson R Currey JD Hynd D 《Journal of biomechanical engineering》2008,130(1):011011
Bone mechanical properties are typically evaluated at relatively low strain rates. However, the strain rate related to traumatic failure is likely to be orders of magnitude higher and this higher strain rate is likely to affect the mechanical properties. Previous work reporting on the effect of strain rate on the mechanical properties of bone predominantly used nonhuman bone. In the work reported here, the effect of strain rate on the tensile and compressive properties of human bone was investigated. Human femoral cortical bone was tested longitudinally at strain rates ranging between 0.14-29.1 s(-1) in compression and 0.08-17 s(-1) in tension. Young's modulus generally increased, across this strain rate range, for both tension and compression. Strength and strain (at maximum load) increased slightly in compression and decreased (for strain rates beyond 1 s(-1)) in tension. Stress and strain at yield decreased (for strain rates beyond 1 s(-1)) for both tension and compression. In general, there seemed to be a relatively simple linear relationship between yield properties and strain rate, but the relationships between postyield properties and strain rate were more complicated and indicated that strain rate has a stronger effect on postyield deformation than on initiation of yielding. The behavior seen in compression is broadly in agreement with past literature, while the behavior observed in tension may be explained by a ductile to brittle transition of bone at moderate to high strain rates. 相似文献
88.
Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake 总被引:4,自引:0,他引:4
Accurate assessment of fat intake is essential to examine the relationships between diet and disease risk but the process of estimating individual intakes of fat quality by dietary assessment is difficult. Tissue and blood fatty acids, because they are mainly derived from the diet, have been used as biomarkers of dietary intake for a number of years. We review evidence from a wide variety of cross-sectional and intervention studies and summarise typical values for fatty acid composition in adipose tissue and blood lipids and changes that can be expected in response to varying dietary intake. Studies in which dietary intake was strictly controlled confirm that fatty acid biomarkers can complement dietary assessment methodologies and have the potential to be used more quantitatively. Factors affecting adipose tissue and blood lipid composition are discussed, such as the physical properties of triacylglycerol, total dietary fat intake and endogenous fatty acid synthesis. The relationship between plasma lipoprotein concentrations and total plasma fatty acid composition, and the use of fatty acid ratios as indices of enzyme activity are also addressed. 相似文献
89.
Prien JM Huysentruyt LC Ashline DJ Lapadula AJ Seyfried TN Reinhold VN 《Glycobiology》2008,18(5):353-366
In an effort to understand the role of molecular glycosylationin cancer a murine model has been used to characterize and fingerprintmalignancies in established cell lines that manifest all thehallmarks of metastatic disease: spontaneous development, localinvasion, intravasation, immune system survival, extravasation,and secondary tumor formation involving liver, kidney, spleen,lung, and brain. Using astrocyte cell controls, we comparedN-linked glycosylation from a nonmetastatic brain tumor cellline and two different metastatic brain tumor cells. Selectedions in each profile were disassembled by ion trap mass spectrometry(MSn) which exhibited multiple structural differences betweeneach tissue. These unique structures were identified withinisomeric compositions as pendant nonreducing termini of di-and trisaccharide fragments, probably transparent to a tandemMS approach but distinctively not to sequential ion trap MSndetection. 相似文献
90.