全文获取类型
收费全文 | 1254篇 |
免费 | 99篇 |
专业分类
1353篇 |
出版年
2023年 | 7篇 |
2022年 | 28篇 |
2021年 | 37篇 |
2020年 | 34篇 |
2019年 | 22篇 |
2018年 | 41篇 |
2017年 | 35篇 |
2016年 | 62篇 |
2015年 | 70篇 |
2014年 | 95篇 |
2013年 | 95篇 |
2012年 | 120篇 |
2011年 | 104篇 |
2010年 | 71篇 |
2009年 | 56篇 |
2008年 | 85篇 |
2007年 | 80篇 |
2006年 | 61篇 |
2005年 | 53篇 |
2004年 | 40篇 |
2003年 | 43篇 |
2002年 | 35篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1981年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1957年 | 1篇 |
1956年 | 2篇 |
1954年 | 2篇 |
排序方式: 共有1353条查询结果,搜索用时 0 毫秒
61.
62.
Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system 总被引:6,自引:0,他引:6
Bemiss CJ Mahon BD Henry A Weaver V Cantorna MT 《Archives of biochemistry and biophysics》2002,402(2):249-254
Interleukin (IL)-2 knockout (KO) mice, which spontaneously develop symptoms of inflammatory bowel disease similar to ulcerative colitis in humans, were made vitamin D deficient (D-) or vitamin D sufficient (D+) or were supplemented with 1,25-dihydroxyvitamin D(3) (1,25D3). 1,25-Dihydroxyvitamin D3 supplementation, but not vitamin D supplementation, reduced the early mortality of IL-2 KO mice. However, colitis severity was not different in D-, D+, or 1,25D3 IL-2 KO mice. Cells from D- IL-2 KO mice produced more interferon (IFN)-gamma than cells from all other mice. Con A-induced proliferation was upregulated in IL-2 KO mice and downregulated in wildtype (WT) mice fed 1,25D3. All other measured immune responses in cells from IL-2 KO mice were unchanged by vitamin D status. In vitro addition of 1,25-dihydroxyvitamin D3 significantly reduced the production of IL-10 and IFN-gamma in cells from D- and D+ WT mice. Conversely, IFN-gamma and IL-10 production in cells from IL-2 KO mice were refractory to in vitro 1,25-dihydroxyvitamin D3 treatments. In the absence of IL-2, vitamin D was ineffective for suppressing colitis and ineffective for the in vitro downregulation of IL-10 or IFN-gamma production. One target of 1,25-dihydroxyvitamin D3 in the immune system is the IL-2 gene. 相似文献
63.
The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy 总被引:36,自引:0,他引:36
Knöll R Hoshijima M Hoffman HM Person V Lorenzen-Schmidt I Bang ML Hayashi T Shiga N Yasukawa H Schaper W McKenna W Yokoyama M Schork NJ Omens JH McCulloch AD Kimura A Gregorio CC Poller W Schaper J Schultheiss HP Chien KR 《Cell》2002,111(7):943-955
Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective role for this Z disc protein in mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T-cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated with dilated cardiomyopathy (DCM) results in a marked defect in T-cap interaction/localization. We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure. 相似文献
64.
Piekorz RP Hoffmeyer A Duntsch CD McKay C Nakajima H Sexl V Snyder L Rehg J Ihle JN 《The EMBO journal》2002,21(4):653-664
TACC3 is a centrosomal/mitotic spindle-associated protein that is highly expressed in a cell cycle-dependent manner in hematopoietic lineage cells. During embryonic development, TACC3 is expressed in a variety of tissues in addition to the hematopoietic lineages. TACC3 deficiency causes an embryonic lethality at mid- to late gestation involving several lineages of cells. Hematopoietic stem cells, while capable of terminal differentiation, are unable to be expanded in vitro or in vivo in reconstitution approaches. Although gross alterations in centrosome numbers and chromosomal segregation are not observed, TACC3 deficiency is associated with a high rate of apoptosis and expression of the p53 target gene, p21(Waf1/Cip1). Hematopoietic stem cell functions, as well as deficiencies in other cell lineages, can be rescued by combining the TACC3 deficiency with p53 deficiency. The results support the concept that TACC3 is a critical component of the centrosome/mitotic spindle apparatus and its absence triggers p53-mediated apoptosis. 相似文献
65.
The influence of the biomechanical parameters of the hip on the outcome of treatment of hips subject to avascular necrosis of the femoral head 总被引:1,自引:0,他引:1
Dolinar D Kralj-Iglic V Iglic A Antolic V Herman S Pavlovcic V 《Cellular & molecular biology letters》2002,7(1):109-111
We were interested in whether or not the biomechanical status of the hip influences the course of avascular necrosis of the femoral head. To investigate this, we used a computer aided system based on a three dimensional mathematical model for determining the stress distribution in the hip joint from standard anteroposterior rentgenographs (X-ray images) of both hips and pelvis. Based on the results of our study, we suggest that the biomechanical parameters of the hip play an important role in the outcome of treatment of hips affected by avascular necrosis of the femoral head. 相似文献
66.
Stadler K Jenei V von Bölcsházy G Somogyi A Jakus J 《Free radical biology & medicine》2003,35(10):1240-1251
The levels of different reactive species, especially those of nitric oxide and peroxynitrite, were determined in streptozotocin-induced diabetic rat tissues, before the development of histopathological damages. Significantly higher steady state free radical concentrations were found in the liver 3 weeks after the onset of diabetes compared to age-matched control groups. Increased nitric oxide levels in diabetic vasculature and kidney decreased the production of detectable reactive oxygen species. High peroxynitrite generation suggested the onset of processes characteristic to premature aging of the endothelium. According to the histopathological results, there were no signs of late complications in the tissues up to 7 weeks after induction of diabetes. These results support the idea that oxidative stress is increased at a very early stage of diabetes and, in particular, that high levels of nitric oxide and peroxynitrite could play a decisive role in the development of late complications in the diabetic vasculature and kidney. 相似文献
67.
Sabine Fischbeck Barbara H. Imruck Maria Blettner Veronika Weyer Harald Binder Sylke R. Zeissig Katharina Emrich Peter Friedrich-Mai Manfred E. Beutel 《PloS one》2015,10(8)
Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S) to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score) and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36%) of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50), higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as ‘in need’, the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life. 相似文献
68.
ádám Z. Lendvai Mathieu Giraudeau Veronika Bókony Frédéric Angelier Olivier Chastel 《Biology letters》2015,11(7)
A crucial problem for every organism is how to allocate energy between competing life-history components. The optimal allocation decision is often state-dependent and mediated by hormones. Here, we investigated how age, a major state variable affects individuals'' hormonal response to a standardized stressor: a trait that may reflect allocation between self-maintenance and reproduction. We caught free-living house sparrows and measured their hormonal (corticosterone) response to capture stress in consecutive years. Using a long-term ringing dataset, we determined the age of the birds, and we partitioned the variation into within- and among-individual age components to investigate the effects of plasticity versus selection or gene flow, respectively, on the stress response. We found large among-individual variation in the birds'' hormone profiles, but overall, birds responded less strongly to capture stress as they grew older. These results suggest that stress responsiveness is a plastic trait that may vary within individuals in an adaptive manner, and natural selection may act on the reaction norms producing optimal phenotypic response in the actual environment and life-history stage. 相似文献
69.
Prabha Sarangi Roland Steinacher Veronika Altmannova Qiong Fu Tanya T. Paull Lumir Krejci Matthew C. Whitby Xiaolan Zhao 《PLoS genetics》2015,11(1)
Protein modifications regulate both DNA repair levels and pathway choice. How each modification achieves regulatory effects and how different modifications collaborate with each other are important questions to be answered. Here, we show that sumoylation regulates double-strand break repair partly by modifying the end resection factor Sae2. This modification is conserved from yeast to humans, and is induced by DNA damage. We mapped the sumoylation site of Sae2 to a single lysine in its self-association domain. Abolishing Sae2 sumoylation by mutating this lysine to arginine impaired Sae2 function in the processing and repair of multiple types of DNA breaks. We found that Sae2 sumoylation occurs independently of its phosphorylation, and the two modifications act in synergy to increase soluble forms of Sae2. We also provide evidence that sumoylation of the Sae2-binding nuclease, the Mre11-Rad50-Xrs2 complex, further increases end resection. These findings reveal a novel role for sumoylation in DNA repair by regulating the solubility of an end resection factor. They also show that collaboration between different modifications and among multiple substrates leads to a stronger biological effect. 相似文献
70.
Manfred E. Beutel Sabine Fischbeck Harald Binder Maria Blettner Elmar Br?hler Katharina Emrich Peter Friedrich-Mai Barbara H. Imruck Veronika Weyer Sylke R. Zeissig 《PloS one》2015,10(1)