全文获取类型
收费全文 | 1543篇 |
免费 | 145篇 |
出版年
2024年 | 3篇 |
2023年 | 13篇 |
2022年 | 47篇 |
2021年 | 81篇 |
2020年 | 50篇 |
2019年 | 66篇 |
2018年 | 69篇 |
2017年 | 50篇 |
2016年 | 74篇 |
2015年 | 116篇 |
2014年 | 114篇 |
2013年 | 123篇 |
2012年 | 138篇 |
2011年 | 135篇 |
2010年 | 73篇 |
2009年 | 55篇 |
2008年 | 91篇 |
2007年 | 75篇 |
2006年 | 50篇 |
2005年 | 52篇 |
2004年 | 50篇 |
2003年 | 38篇 |
2002年 | 36篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有1688条查询结果,搜索用时 15 毫秒
161.
Millucci L Paccagnini E Ghezzi L Bernardini G Braconi D Laschi M Consumi M Spreafico A Tanganelli P Lupetti P Magnani A Santucci A 《PloS one》2011,6(7):e21870
Aims
Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis.Methods and Results
A significant prevalence (85%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA.Conclusions
We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis. 相似文献162.
Knutson KL Galli G Zhao X Mattingly M Cizza G;NIDDK Sleep Extension Study 《Obesity (Silver Spring, Md.)》2011,19(12):2433-2435
Previous research in lean subjects has found lower leptin levels associated with shorter sleep duration. Since leptin levels are higher and some of the actions of leptin are impaired in obese individuals, one cannot assume that sleep will be similarly associated with leptin in obese individuals. The aim of this paper was to examine the cross-sectional association between habitual sleep duration and quality and plasma leptin levels in a sample of 80 obese men and premenopausal women aged 18-50 years. Leptin levels (ng/ml) were assayed on a fasting blood sample taken in the morning. We calculated a relative leptin level by dividing leptin by body fat percentage. Sleep duration and sleep efficiency were measured by 2 weeks of wrist actigraphy and respiratory disturbance index (RDI), a measure of sleep disordered breathing, was assessed by a portable screening device on a single night. Mean leptin levels and body fat percentage were higher in women than men (P < 0.001), however, mean RDI was higher in men (P = 0.01). There were no significant associations between relative leptin level and any of the sleep measures, including sleep duration, sleep efficiency, and sleep disordered breathing. There was also no difference between men and women in the association between sleep and leptin. In conclusion, contrary to what has been reported in other studies, measures of sleep duration and quality were not associated with leptin levels in our sample of obese adults. 相似文献
163.
164.
165.
Modulation of osteoclastogenesis in porcine bone marrow cultures by quercetin and rutin 总被引:3,自引:0,他引:3
Rassi CM Lieberherr M Chaumaz G Pointillart A Cournot G 《Cell and tissue research》2005,319(3):383-393
Flavonols, in contrast to soybean isoflavones, are the most abundant phytoestrogens in western diets, being present in onions, beans, fruits, red wine, and tea. They may protect against atherosclerosis, inhibit certain cancer cell types, and reduce bone resorption. The most widely distributed flavonol is quercetin, which occurs mainly as its glycoside, rutin, but data are very scarce regarding the precise mechanism of action of these compounds on bone-resorbing cells at concentrations similar to those detected in human plasma. We have therefore investigated the effects of nanomolar concentrations of quercetin and rutin on the development and activity of osteoclasts in vitro compared with the effects of 17-estradiol. Nonadherent porcine bone marrow cells were cultured on dentine slices in the presence of 10 nM 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), with or without 10 nM quercetin, 10 nM rutin or 10 nM 17-estradiol for 11 days. Multinuclear TRAP+ cells that resorbed dentine (osteoclasts) developed in the presence of 1,25(OH)2D3, but their number was significantly reduced by quercetin, rutin, and 17-estradiol (P < 0.05). Like 17-estradiol, both flavonols also significantly reduced resorption (P<0.05) as assessed by the size of pits resorbed on dentine slices. Osteoclasts and osteoclast progenitors contained estrogen receptor (ER), ER, and RANK proteins. Both flavonols increased nuclear ER protein and decreased ER protein of osteoclast progenitors. Moreover, rutin reduced RANK protein, whereas 17-oestradiol and quercetin promoted apoptosis by cleavage of caspase-8 and caspase-3. All the effects of flavonols were reversed by 1 M ICI 182,780, an estrogen antagonist. Thus, the anti-resorbing properties of flavonols are mainly mediated by ER proteins through the inhibition of RANK protein or the activation of caspases.C.M.R. was supported by a grant from CAPES (Department of Education, Brasilia, Brasil). 相似文献
166.
Menconi G 《Bulletin of mathematical biology》2005,67(4):737-759
We introduce a novel method to analyse complete genomes and recognise some distinctive features by means of an adaptive compression
algorithm, which is not DNA-oriented, based on the Lempel-Ziv scheme. We study the Information Content as a function of the
number of symbols encoded by the algorithm and we analyse the dictionary created by the algorithm. Preliminary results are
shown concerning regions showing a sublinear type of information growth, which is strictly connected to the presence of highly
repetitive subregions that might be supposed to have a regulatory function within the genome. 相似文献
167.
Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Adinolfi E Callegari MG Ferrari D Bolognesi C Minelli M Wieckowski MR Pinton P Rizzuto R Di Virgilio F 《Molecular biology of the cell》2005,16(7):3260-3272
P2X7 is a bifunctional receptor (P2X7R) for extracellular ATP that, depending on the level of activation, forms a cation-selective channel or a large conductance nonselective pore. The P2X7R has a strong proapoptotic activity but can also support growth. Here, we describe the mechanism involved in growth stimulation. Transfection of P2X7R increases resting mitochondrial potential (delta psi(mt)), basal mitochondrial Ca2+ ([Ca2+]mt), intracellular ATP content, and confers ability to grow in the absence of serum. These changes require a full pore-forming function, because they are abolished in cells transfected with a mutated P2X7R that retains channel activity but cannot form the nonselective pore, and depend on an autocrine/paracrine tonic stimulation by secreted ATP. On the other hand, sustained stimulation of P2X7R causes a delta psi(mt) drop, a large increase in [Ca2+]mt, mitochondrial fragmentation, and cell death. These findings reveal a hitherto undescribed mechanism for growth stimulation by a plasma membrane pore. 相似文献
168.
Lescai F Conti L Bartolozzi M Ramazzotti G Mazzi M Sarnicola V Franceschi C 《Biochemical and biophysical research communications》2005,332(1):95-100
We tested the hypothesis that the genetic capability to mount an inflammatory response might contribute to the inter-individual variability of limbal stem cell graft (LSCG) outcome. Two functional polymorphisms in the IL-6 and TNF-alpha promoter regions were genotyped in 35 patients. A new score system (clinical assessment score, CAS) was set up in order to classify patients' clinical profile, and the main parameters relevant for LSCG as well as for the follow-up of the patients. Patients carrying at both loci a genotype associated with a lower production of both cytokines were classified as "low producers" (LP), while all the others were classified as "intermediate or high producers" (HP). LP patients did not show any difference in CAS before and after transplantation while a significant difference was present in HP patients. A similar trend was evident in the 35 months of follow-up. Polymorphisms of IL-6 and TNF-alpha can be used to identify subgroups of patients with higher risk of unsuccessful outcome. 相似文献
169.
Cobellis G Lombardi M Scarpa D Izzo G Fienga G Meccariello R Pierantoni R Fasano S 《Biology of reproduction》2005,72(5):1101-1108
Using an anti-Fos family member antibody, we have previously described in Rana esculenta testis the presence of a nuclear, 43 kDa protein that we hypothesized to be Fra1. With the assistance of an antibody against Fra1 that does not cross-react with other Fos family members, here we report data on Fra1 expression, localization, and putative activity in Rana esculenta testis during its annual reproductive cycle. Western blot analysis confirms that the nuclear, 43 kDa protein is Fra1. Immunocytochemistry validates the Western blot results and shows cytoplasmic and nuclear immunostaining of Fra1 in peritubular myoid cells, efferent ducts, and blood vessels. We report for the first time in a vertebrate, experimental evidence showing that the expression of Fra1 is related to peritubular myoid cells during sperm transport from the tubular compartment to efferent ducts. 相似文献
170.
Telomere attrition and other forms of telomere damage can activate the ATM kinase pathway. What generates the DNA damage signal at mammalian chromosome ends or at other double-strand breaks is not known. Telomere dysfunction is often accompanied by disappearance of the 3' telomeric overhang, raising the possibility that DNA degradation could generate the structure that signals. Here we address these issues by studying telomere structure after conditional deletion of mouse TRF2, the protective factor at telomeres. Upon removal of TRF2 from TRF2(F/-) p53-/- mouse embryo fibroblasts, a telomere damage response is observed at most chromosome ends. As expected, the telomeres lose the 3' overhang and are processed by the non-homologous end-joining pathway. Non-homologous end joining of telomeres was abrogated in DNA ligase IV-deficient (Lig4-/-) cells. Unexpectedly, the telomeres of TRF2-/- Lig4-/- p53-/- cells persisted in a free state without undergoing detectable DNA degradation. Notably, the telomeres retained their 3' overhangs, but they were recognized as sites of DNA damage, accumulating the DNA damage response factors 53BP1 and gamma-H2AX, and activating the ATM kinase. Thus, activation of the ATM kinase pathway at chromosome ends does not require overhang degradation or other overt DNA processing. 相似文献