全文获取类型
收费全文 | 785篇 |
免费 | 70篇 |
专业分类
855篇 |
出版年
2023年 | 2篇 |
2022年 | 14篇 |
2021年 | 24篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 31篇 |
2015年 | 45篇 |
2014年 | 54篇 |
2013年 | 58篇 |
2012年 | 89篇 |
2011年 | 63篇 |
2010年 | 43篇 |
2009年 | 45篇 |
2008年 | 52篇 |
2007年 | 44篇 |
2006年 | 42篇 |
2005年 | 31篇 |
2004年 | 34篇 |
2003年 | 28篇 |
2002年 | 25篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 10篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 5篇 |
1982年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有855条查询结果,搜索用时 15 毫秒
81.
Since the discovery that 43 kDa TAR DNA binding protein (TDP-43) is involved in neurodegeneration, studies of this protein have focused on the global effects of TDP-43 expression modulation on cell metabolism and survival. The major difficulty with these global searches, which can yield hundreds to thousands of variations in gene expression level and/or mRNA isoforms, is our limited ability to separate specific TDP-43 effects from secondary dysregulations occurring at the gene expression and various mRNA processing steps. In this review, we focus on two biochemical properties of TDP-43: its ability to bind RNA and its protein-protein interactions. In particular, we overview how these two properties may affect potentially very important processes for the pathology, from the autoregulation of TDP-43 to aggregation in the cytoplasmic/nuclear compartments. 相似文献
82.
83.
Claudio Muscari Emanuele Giordano Francesca Bonafè Marco Govoni Alice Pasini Carlo Guarnieri 《Journal of biomedical science》2013,20(1):63
The efficiency of regenerative medicine can be ameliorated by improving the biological performances of stem cells before their transplantation. Several ex-vivo protocols of non-damaging cell hypoxia have been demonstrated to significantly increase survival, proliferation and post-engraftment differentiation potential of stem cells. The best results for priming cultured stem cells against a following, otherwise lethal, ischemic stress have been obtained with brief intermittent episodes of hypoxia, or anoxia, and reoxygenation in accordance with the extraordinary protection afforded by the conventional maneuver of ischemic preconditioning in severely ischemic organs. These protocols of hypoxic preconditioning can be rather easily reproduced in a laboratory; however, more suitable pharmacological interventions inducing stem cell responses similar to those activated in hypoxia are considered among the most promising solutions for future applications in cell therapy. Here we want to offer an up-to-date review of the molecular mechanisms translating hypoxia into beneficial events for regenerative medicine. To this aim the involvement of epigenetic modifications, microRNAs, and oxidative stress, mainly activated by hypoxia inducible factors, will be discussed. Stem cell adaptation to their natural hypoxic microenvironments (niche) in healthy and neoplastic tissues will be also considered. 相似文献
84.
Jennifer Kernan Thomas Bonacci Michael J. Emanuele 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(12):1924-1933
The cell cycle is principally controlled by Cyclin Dependent Kinases (CDKs), whose oscillating activities are determined by binding to Cyclin coactivators. Cyclins exhibit dynamic changes in abundance as cells pass through the cell cycle. The sequential, timed accumulation and degradation of Cyclins, as well as many other proteins, imposes order on the cell cycle and contributes to genome maintenance. The destruction of many cell cycle regulated proteins, including Cyclins A and B, is controlled by a large, multi-subunit E3 ubiquitin ligase termed the Anaphase Promoting Complex/Cyclosome (APC/C). APC/C activity is tightly regulated during the cell cycle. Its activation state increases dramatically in mid-mitosis and it remains active until the end of G1 phase. Following its mandatory inactivation at the G1/S boundary, APC/C activity remains low until the subsequent mitosis. Due to its role in guarding against the inappropriate or untimely accumulation of Cyclins, the APC/C is a core component of the cell cycle oscillator. In addition to the regulation of Cyclins, APC/C controls the degradation of many other substrates. Therefore, it is vital that the activity of APC/C itself be tightly guarded. The APC/C is most well studied for its role and regulation during mitosis. However, the APC/C also plays a similarly important and conserved role in the maintenance of G1 phase. Here we review the diverse mechanisms counteracting APC/C activity throughout the cell cycle and the importance of their coordinated actions on cell growth, proliferation, and disease. 相似文献
85.
NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome 总被引:7,自引:0,他引:7 下载免费PDF全文
De Luca A Bottillo I Sarkozy A Carta C Neri C Bellacchio E Schirinzi A Conti E Zampino G Battaglia A Majore S Rinaldi MM Carella M Marino B Pizzuti A Digilio MC Tartaglia M Dallapiccola B 《American journal of human genetics》2005,77(6):1092-1101
Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11-27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals. 相似文献
86.
Mariella Baratti Emanuele Goti Giuseppe Messana 《Journal of experimental marine biology and ecology》2005,315(2):225-234
Sphaeroma terebrans Bate 1866 is a marine isopod belonging to the large family Sphaeromatidae, which normally colonises the aerial roots of the mangrove genus Rhizophora in tropical and subtropical areas. S. terebrans is part of a group of species whose complete life cycle occurs within the same mangrove wood. In this paper, we provide clear evidence of significant genetic differentiation among geographic populations of the taxon S. terebrans. The consistently low internal variation and the large interpopulation distances indicate that almost all the mitochondrial variation (cytochrome oxidase I) in S. terebrans is apportioned among populations rather than within them. The mean haplotype diversity (h) is 0.71%, and the mean nucleotide diversity (π) is 0.34%. The Minimum Spanning Tree (MST) reveals a complex pattern: three principal haplotype groups corresponding to the geographic locations investigated are distributed in a network. This suggests an ancient evolutionary history and very restricted gene flow between populations. The large genetic distances between the populations of S. terebrans could suggest that this taxon is not a single species but a species complex whose taxonomic status must be revaluated. 相似文献
87.
The study of marriage seasonality of populations with different socioeconomic backgrounds may contribute to the better understanding their reproductive behaviours. This study analyses the monthly distribution of marriages in the 19th century in four agricultural villages and four pastoral villages on the island of Sardinia (Italy). The data were derived from 7340 marriage acts (3571 for the four agricultural villages and 3769 for the four pastoral villages). The aim is to ascertain whether the Sardinian agricultural and pastoral communities followed the matrimonial models reported for contemporary Italy and Europe and whether there was a change in the monthly distribution of marriages between the two halves of the 19th century. The results suggest that the marriage seasonality of the Sardinian farmers and shepherds was very similar to the patterns shown in the 19th century by Italian and European agricultural and pastoral communities. The Sardinian farmers preferred to marry in autumn-winter, while the Sardinian shepherds had a very high concentration of marriages in summer-autumn. Both communities avoided marriages in the Advent and Easter periods and in the month of May (dedicated to the Virgin Mary), and the farmers also in August (also dedicated to the Virgin Mary). Despite a certain seasonal stability, there was a significant change in the monthly distribution of marriages between the two halves of the 19th century in both the agricultural and pastoral communities, probably due to a series of laws that transformed the centuries-old socioeconomic system of Sardinia in the second half of the century. 相似文献
88.
89.
In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on misunderstandings concerning the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk. 相似文献
90.
Emanuele Sanna Lucia Palmas Maria Renata Soro Elisabetta Vallascas Alessandro De Micco 《HOMO》2012,63(1):67-75
There exist few standards of head length and breadth from childhood to adulthood in Europoid populations. Moreover, such standards are based on samples that cannot be used as references for all populations since they were taken from different ethnic groups and from different periods. The aims of this study were: (1) to test whether standards derived from North Americans of European extraction can be used to assess the Sardinian population; and (2) to produce growth charts for head length and breadth for Sardinian males and females from 3 to 22 years of age.The cross sectional sample consisted of 9,721 subjects of Sardinian origin (4,884 males and 4,837 females), aged 3–22 years, measured from 1998 to 2008. Growth percentiles were produced with the LMS method. The mean values for each sex in each age class (3–18 years) are almost always significantly lower for both head length and breadth than the corresponding North American values. The exceptions are the head length of boys of 14 years and girls of 16–18 years where values for Sardinians are lower, but not significantly so. The results show that the North American standards are not appropriate for the assessment of Sardinian children. For the Sardinian population, specific regional growth charts should be used to correctly evaluate the normal range and the cut-off points of the extreme percentiles. 相似文献