全文获取类型
收费全文 | 529篇 |
免费 | 53篇 |
出版年
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 13篇 |
2014年 | 21篇 |
2013年 | 23篇 |
2012年 | 28篇 |
2011年 | 26篇 |
2010年 | 19篇 |
2009年 | 16篇 |
2008年 | 17篇 |
2007年 | 27篇 |
2006年 | 20篇 |
2005年 | 17篇 |
2004年 | 21篇 |
2003年 | 14篇 |
2002年 | 17篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 17篇 |
1997年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 13篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 12篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1971年 | 5篇 |
1968年 | 4篇 |
1965年 | 3篇 |
1964年 | 3篇 |
1961年 | 4篇 |
排序方式: 共有582条查询结果,搜索用时 15 毫秒
501.
502.
Emily Fitzherbert Toby Gardner Tim R. B. Davenport Tim Caro 《African Journal of Ecology》2006,44(3):353-362
We sampled butterflies in six different habitat types in and around Katavi National Park, a remote reserve consisting primarily of miombo woodland and seasonal lakes in western Tanzania. Blendon traps set for 531 trap days and 143 h of butterfly netting at 35 sites yielded 186 species from five families over a 4‐month period during the wet season. Eight of these species constituted possible range extensions. Butterfly abundance and species richness were low in cultivated habitats but high in open riverine habitats; many butterfly species were found only in seasonally flooded grassland. This study constitutes the first butterfly species inventory from this poorly‐known national park, shows that protection of dry season water sources provides an important conservation service for invertebrates as well as large mammals, and that increased cultivation outside miombo parks can reduce local butterfly diversity. 相似文献
503.
Ee Phie Tan Sarah Caro Anish Potnis Christopher Lanza Chad Slawson 《The Journal of biological chemistry》2013,288(38):27085-27099
Any defects in the correct formation of the mitotic spindle will lead to chromosomal segregation errors, mitotic arrest, or aneuploidy. We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a post-translational modification of serine and threonine residues in nuclear and cytoplasmic proteins, regulates spindle function. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, the mitotic spindle is incorrectly assembled. Chromosome condensation and centrosome assembly is impaired in these cells. The disruption in spindle architecture is due to a reduction in histone H3 phosphorylation by Aurora kinase B. However, gain of function cells treated with the O-GlcNAcase inhibitor Thiamet-G restored the assembly of the spindle and partially rescued histone phosphorylation. Together, these data suggest that the coordinated addition and removal of O-GlcNAc, termed O-GlcNAc cycling, regulates mitotic spindle organization and provides a potential new perspective on how O-GlcNAc regulates cellular events. 相似文献
504.
A. Porzionato M.M. Sfriso V. Macchi A. Rambaldo G. Lago L. Lancerotto V. Vindigni R. De Caro 《European journal of histochemistry : EJH》2013,57(1)
Homologous tissues, such as adipose tissue, may be an interesting source of acellular scaffolds, maintaining a complex physiological three-dimensional (3D) structure, to be recellularized with autologous cells. The aim of the present work is to evaluate the possibility of obtaining homologous acellular scaffolds from decellularization of the omentum, which is known to have a complex vascular network. Adult rat and human omenta were treated with an adapted decellularization protocol involving mechanical rupture (freeze-thaw cycles), enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid extraction (2-propanol). Histological staining confirmed the effectiveness of decellularization, resulting in cell-free scaffolds with no residual cells in the matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue. The vascular structures in the tissue were still visible, with preservation of collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34 immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells. Fat-rich and well vascularized omental tissue may be decellularized to obtain complex 3D scaffolds preserving tissue architecture potentially suitable for recellularization. Further analyses are necessary to verify the possibility of recolonization of the scaffold by adipose-derived stem cells in vitro and then in vivo after re implantation, as already known for homologus implants in regenerative processes.Key words: omentum, scaffold, decellularization, adipose tissue engineering, regenerative medicine, microvascularization 相似文献
505.
Susi Zara Marianna De Colli Monica Rapino Valentina Di Valerio Guya Diletta Marconi Amelia Cataldi Veronica Macchi Raffaele De Caro Andrea Porzionato 《Histochemistry and cell biology》2013,140(5):575-583
Premature newborns are frequently exposed to hyperoxia ventilation and some literature data indicate the possibility of hyperoxia-induced myocardial damage. Since nuclear factor κB (NF-κB) is a crucial signaling molecule involved in physiological response to hyperoxia in different cell types as well as in various tissues, our attention has been focused on the role played by NF-κB pathway in response to moderate and severe hyperoxia exposure in rat neonatal heart tissue. Akt and IκBα levels, involved in NF-κB activation, along with the balance between apoptotic and survival pathways have also been investigated. Experimental design of the study has involved exposure of newborn rats to room air (controls), 60 % O2 (moderate hyperoxia), or 95 % O2 (severe hyperoxia) for the first two postnatal weeks. Morphological analysis shows a less compact tissue in rat heart exposed to moderate hyperoxia and a decreased number of nuclei in samples exposed to severe hyperoxia. A significant increase of NF-κB positive nuclei percentage and p-IκBα expression in samples exposed to 95 % hyperoxia compared to control and to 60 % hyperoxia is evidenced; in parallel, an increase of pAkt/Akt ratio in both samples exposed to 95 and 60 % hyperoxia is shown. Furthermore, a more evident cytochrome c/Apaf-1 immunocomplex and a decreased Bcl2 expression in 95 % hyperoxia-exposed sample compared to 60 % exposed one is evidenced. In conclusion, our findings suggest the involvement of the NF-κB pathway and Akt signaling in the mechanisms of myocardial hyperoxic damage in the newborns, with particular reference to the induction of oxidative stress-related apoptosis. 相似文献
506.
Barbara Koeck Josep Alós Anthony Caro Reda Neveu Romain Crec'hriou Gilles Saragoni Philippe Lenfant 《PloS one》2013,8(7)
Artificial reefs are used by many fisheries managers as a tool to mitigate the impact of fisheries on coastal fish communities by providing new habitat for many exploited fish species. However, the comparison between the behavior of wild fish inhabiting either natural or artificial habitats has received less attention. Thus the spatio-temporal patterns of fish that establish their home range in one habitat or the other and their consequences of intra-population differentiation on life-history remain largely unexplored. We hypothesize that individuals with a preferred habitat (i.e. natural vs. artificial) can behave differently in terms of habitat use, with important consequences on population dynamics (e.g. life-history, mortality, and reproductive success). Therefore, using biotelemetry, 98 white seabream (Diplodus sargus) inhabiting either artificial or natural habitats were tagged and their behavior was monitored for up to eight months. Most white seabreams were highly resident either on natural or artificial reefs, with a preference for the shallow artificial reef subsets. Connectivity between artificial and natural reefs was limited for resident individuals due to great inter-habitat distances. The temporal behavioral patterns of white seabreams differed between artificial and natural reefs. Artificial-reef resident fish had a predominantly nocturnal diel pattern, whereas natural-reef resident fish showed a diurnal diel pattern. Differences in diel behavioral patterns of white seabream inhabiting artificial and natural reefs could be the expression of realized individual specialization resulting from differences in habitat configuration and resource availability between these two habitats. Artificial reefs have the potential to modify not only seascape connectivity but also the individual behavioral patterns of fishes. Future management plans of coastal areas and fisheries resources, including artificial reef implementation, should therefore consider the potential effect of habitat modification on fish behavior, which could have key implications on fish dynamics. 相似文献
507.
Florentine S. Hilbers Caro M. Meijers Jeroen F. J. Laros Michiel van Galen Nicoline Hoogerbrugge Hans F. A. Vasen Petra M. Nederlof Juul T. Wijnen Christi J. van Asperen Peter Devilee 《PloS one》2013,8(1)
The bulk of familial breast cancer risk (∼70%) cannot be explained by mutations in the known predisposition genes, primarily BRCA1 and BRCA2. Underlying genetic heterogeneity in these cases is the probable explanation for the failure of all attempts to identify further high-risk alleles. While exome sequencing of non-BRCA1/2 breast cancer cases is a promising strategy to detect new high-risk genes, rational approaches to the rigorous pre-selection of cases are needed to reduce heterogeneity. We selected six families in which the tumours of multiple cases showed a specific genomic profile on array comparative genomic hybridization (aCGH). Linkage analysis in these families revealed a region on chromosome 4 with a LOD score of 2.49 under homogeneity. We then analysed the germline DNA of two patients from each family using exome sequencing. Initially focusing on the linkage region, no potentially pathogenic variants could be identified in more than one family. Variants outside the linkage region were then analysed, and we detected multiple possibly pathogenic variants in genes that encode DNA integrity maintenance proteins. However, further analysis led to the rejection of all variants due to poor co-segregation or a relatively high allele frequency in a control population. We concluded that using CGH results to focus on a sub-set of families for sequencing analysis did not enable us to identify a common genetic change responsible for the aggregation of breast cancer in these families. Our data also support the emerging view that non-BRCA1/2 hereditary breast cancer families have a very heterogeneous genetic basis. 相似文献
508.
Anderson KM 《Biometrical journal. Biometrische Zeitschrift》2007,49(3):337-345
We present optimized group sequential designs where testing of a single parameter theta is of interest. We require specification of a loss function and of a prior distribution for theta. For the examples presented, we pre-specify Type I and II error rates and minimize the expected sample size over the prior distribution for theta. Minimizing the square of sample size rather than the sample size is found to produce designs with slightly less aggressive interim stopping rules and smaller maximum sample sizes with essentially identical expected sample size. We compare optimal designs using Hwang-Shih-DeCani and Kim-DeMets spending functions to fully optimized designs not restricted by a spending function family. In the examples selected, we also examine when there might be substantial benefit gained by adding an interim analysis. Finally, we provide specific optimal asymmetric spending function designs that should be generally useful and simply applied when a design with minimal expected sample size is desired. 相似文献
509.
Parenti A Porzionato A Pizzi S Guzzardo V Fassina G Macchi V Ninfo V De Caro R 《Histology and histopathology》2007,22(9):989-995
The aim of the present study was to evaluate the tissue expression of squamous cell carcinoma antigen (SCCA) in oesophageal dysplasia and squamous cell carcinoma (SCC) with reference to its clinico-pathologic and prognostic significance. Immunohistochemistry using SCCA polyclonal antibody was performed on SCCs from 61 surgical oesophagectomies. Fifteen cases of low-grade dysplasia (LGD) and 37 non-coexistent high-grade dysplasia (HGD) were also sampled from these materials, together with sixteen chronic cases of oesophagitis. SCCA immunoreactivity was present in the maturative compartments of all normal epithelia and oesophagitis. LGDs showed no SCCA immunoreactivity in the dysplastic proliferative component but only in the superficial normal layers. In 94.6% of HGDs, no SCCA immunoreactivity was detected throughout the thickness of the epithelium. In SCCs, SCCA expression higher than 25% was found in 54% of cases. SCCA positivity showed an inverse correlation with histological grade, whereas no statistically significant correlation was found with TNM classifications, stage, or survival. SCCA is not expressed in early oesophageal carcinogenesis but, in SCC, it represents an indicator of histologic differentiation. In differentiated SCC, SCCA may represent a negative factor for cancer invasiveness, through inhibition of proteases. 相似文献
510.
Thomas D Walko III Valentina Di Caro Jon Piganelli Timothy R Billiar Robert SB Clark Rajesh K Aneja 《Molecular medicine (Cambridge, Mass.)》2014,20(1):612-624
Pathophysiological conditions that lead to the release of the prototypic damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) also result in activation of poly(ADP-ribose) polymerase 1 (PARP1; now known as ADP-ribosyl transferase 1 [ARTD1]). Persistent activation of PARP1 promotes energy failure and cell death. The role of poly(ADP-ribosyl)ation in HMGB1 release has been explored previously; however, PARP1 is a versatile enzyme and performs several other functions including cross-talk with another nicotinamide adenine dinucleotide- (NAD+) dependent member of the Class III histone deacetylases (HDACs), sirtuin-1 (SIRT1). Previously, it has been shown that the hyperacetylation of HMGB1 is a seminal event prior to its secretion, a process that also is dependent on HDACs. Therefore, in this study, we seek to determine if PARP1 inhibition alters LPS-mediated HMGB1 hyperacetylation and subsequent secretion due to its effect on SIRT1. We demonstrate in an in vitro model that LPS treatment leads to hyperacetylated HMGB1 with concomitant reduction in nuclear HDAC activity. Treatment with PARP1 inhibitors mitigates the LPS-mediated reduction in nuclear HDAC activity and decreases HMGB1 acetylation. By utilizing an NAD+-based mechanism, PARP1 inhibition increases the activity of SIRT1. Consequently, there is an increased nuclear retention and decreased extracellular secretion of HMGB1. We also demonstrate that PARP1 physically interacts with SIRT1. Further confirmation of this data was obtained in a murine model of sepsis, that is, administration of PJ-34, a specific PARP1 inhibitor, led to decreased serum HMGB1 concentrations in mice subjected to cecal ligation and puncture (CLP) as compared with untreated mice. In conclusion, our study provides new insights in understanding the molecular mechanisms of HMGB1 secretion in sepsis. 相似文献