全文获取类型
收费全文 | 430篇 |
免费 | 27篇 |
出版年
2024年 | 2篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 4篇 |
2017年 | 9篇 |
2016年 | 9篇 |
2015年 | 16篇 |
2014年 | 21篇 |
2013年 | 31篇 |
2012年 | 35篇 |
2011年 | 42篇 |
2010年 | 24篇 |
2009年 | 23篇 |
2008年 | 21篇 |
2007年 | 30篇 |
2006年 | 22篇 |
2005年 | 18篇 |
2004年 | 18篇 |
2003年 | 15篇 |
2002年 | 18篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1966年 | 3篇 |
1965年 | 2篇 |
1927年 | 1篇 |
1917年 | 1篇 |
1915年 | 1篇 |
1914年 | 1篇 |
排序方式: 共有457条查询结果,搜索用时 78 毫秒
121.
122.
Ilaria Parenti Davide Rovina Maura Masciadri Anna Cereda Jacopo Azzollini Chiara Picinelli Giuseppe Limongelli Palma Finelli Angelo Selicorni Silvia Russo Cristina Gervasini Lidia Larizza 《Epigenetics》2014,9(7):973-979
Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, limb anomalies, and growth and cognitive deficits. Mutations in genes encoding subunits (SMC1A, SMC3, RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex account for approximately 65% of clinically diagnosed CdLS cases. The SMC1A gene (Xp11.22), responsible for 5% of CdLS cases, partially escapes X chromosome inactivation in humans and the allele on the inactive X chromosome is variably expressed. In this study, we evaluated overall and allele-specific SMC1A expression. Real-time PCR analysis conducted on 17 controls showed that SMC1A expression in females is 50% higher than in males. Immunoblotting experiments confirmed a 44% higher protein level in healthy females than in males, and showed no significant differences in SMC1A protein levels between controls and patients. Pyrosequencing was used to assess the reciprocal level of allelic expression in six female carriers of different SMC1A mutations and 15 controls who were heterozygous at a polymorphic transcribed SMC1A locus. The two alleles were expressed at a 1:1 ratio in the control group and at a 2:1 ratio in favor of the wild type allele in the test group. Since a dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. An extension of this study to a larger cohort containing mild to borderline cases could enhance our understanding of the clinical spectrum of SMC1A-linked CdLS. 相似文献
123.
This study was undertaken to characterize the programmed cell death (PCD) processes that occur during detached and natural on-plant senescence and correlate them with the expression of putative regulatory genes that may be involved in the process. DNA fragmentation and TUNEL analysis of broccoli florets showed that DNA was processed into fragments of approximately 180 bp after 48 h of harvest-induced tissue senescence. Characteristic laddering patterns were also visible in Arabidopsis leaves undergoing natural on-plant senescence and during detached senescence. Several recently isolated plant proteins have been assigned a PCD role, for example, the zinc finger containing protein, LSD1 (lesion simulating disease); Bax inhibitor (BI); and serine palmitoyltransferase (SPT), an enzyme in the sphingolipid signalling pathway. Two cDNAs encoding each of these proteins were isolated from broccoli (BoBI-1, BoBI-2, BoLSD1, BoLSD2, BoSPT1, BoSPT2), and the mRNAs increased during harvest-induced senescence in floret tissue. Expression of the Arabidopsis homologues (AtBI-1, AtLSD1, AtSPT1) were also characterized during detached leaf senescence in Arabidopsis leaves. AtBI-1 expression was constitutively expressed during detached senescence, AtLSD1 expression remained constitutively low, and AtSPT1 expression increased during detached senescence. 相似文献
124.
Lewis TA Bayless L DiPesa AJ Eckman JB Gillard M Libertine L Scannell RT Wypij DM Young MA 《Bioorganic & medicinal chemistry letters》2005,15(4):1083-1085
A series of N-hydroxycarbamates containing a histaminergic H(1) receptor antagonist pharmacophore was synthesized. In vitro assays determined the compounds had both histaminergic binding and 5-lipoxygenase inhibiting activities comparable to the corresponding N-hydroxyurea analog. Animal models demonstrated antihistaminergic and the 5-lipopxygenase inhibitory activity, with the N-hydroxyurea analog having a better overall profile. 相似文献
125.
Not so ancient: the extant crown group of Nothofagus represents a post-Gondwanan radiation 总被引:2,自引:0,他引:2
This study uses a molecular-dating approach to test hypotheses about the biogeography of Nothofagus. The molecular modelling suggests that the present-day subgenera and species date from a radiation that most likely commenced between 55 and 40 Myr ago. This rules out the possibility of a reconciled all-vicariance hypothesis for the biogeography of extant Nothofagus. However, the molecular dates for divergences between Australasian and South American taxa are consistent with the rifting of Australia and South America from Antarctica. The molecular dates further suggest a dispersal of subgenera Lophozonia and Fuscospora between Australia and New Zealand after the onset of the Antarctic Circumpolar Current and west wind drift. It appears likely that the New Caledonian lineage of subgenus Brassospora diverged from the New Guinean lineage elsewhere, prior to colonizing New Caledonia.The molecular approach strongly supports fossil-based estimates that Nothofagus diverged from the rest of Fagales more than 84 Myr ago. However, the mid-Cenozoic estimate for the diversification of the four extant subgenera conflicts with the palynological interpretation because pollen fossils, attributed to all four extant subgenera, were widespread across the Weddellian province of Gondwana about 71 Myr ago. The discrepancy between the pollen and molecular dates exists even when confidence intervals from several sources of error are taken into account. In contrast, the molecular age estimates are consistent with macrofossil dates. The incongruence between pollen fossils and molecular dates could be resolved if the early pollen types represent extinct lineages, with similar types later evolving independently in the extant lineages. 相似文献
126.
Early evolution of the human immunodeficiency virus type 1 subtype C epidemic in rural Malawi 下载免费PDF全文
McCormack GP Glynn JR Crampin AC Sibande F Mulawa D Bliss L Broadbent P Abarca K Pönnighaus JM Fine PE Clewley JP 《Journal of virology》2002,76(24):12890-12899
We have tracked the early years of the evolution of the human immunodeficiency virus type 1 (HIV-1) epidemic in a rural district of central east Africa from the first documented introductions of subtypes A, D, and C to the present predominance of subtype C. The earliest subtype C sequences ever reported are described. Blood samples were collected on filter papers from 1981 to 1984 and from 1987 to 1989 from more than 44,000 individuals living in two areas of Karonga District, Malawi. These samples included HIV-1-positive samples from 200 people. In 1982 to 1984, HIV-1 subtypes A, C, and D were all present, though in small numbers. By 1987 to 1989, 152 (90%) of a total of 168 sequences were subtype C and AC, AD, and DC recombinants had emerged. Four of the subtype C sequences from 1983 to 1984 were closely related and were found at the base of a large cluster of low diversity that by the late 1980s accounted for 40% of C sequences. The other two early C sequences fell into a separate and more diverse cluster. Three other clusters containing sequences from the late 1980s were identified. Each cluster contained at least one sample from a person who had recently arrived in the district. From 18 HIV-1-positive spouse pairs, 12 very closely related pairs of sequences were identified. We conclude that there were multiple introductions of HIV-1 with limited spread, followed by explosive growth of a subtype C cluster, probably arising from a single introduction in or before 1983. 相似文献
127.
Xin Huang Alyssa Lyn Fortier Alec J Coffman Travis J Struck Megan N Irby Jennifer E James Jos E Len-Burguete Aaron P Ragsdale Ryan N Gutenkunst 《Molecular biology and evolution》2021,38(10):4588
The effect of a mutation on fitness may differ between populations depending on environmental and genetic context, but little is known about the factors that underlie such differences. To quantify genome-wide correlations in mutation fitness effects, we developed a novel concept called a joint distribution of fitness effects (DFE) between populations. We then proposed a new statistic w to measure the DFE correlation between populations. Using simulation, we showed that inferring the DFE correlation from the joint allele frequency spectrum is statistically precise and robust. Using population genomic data, we inferred DFE correlations of populations in humans, Drosophila melanogaster, and wild tomatoes. In these species, we found that the overall correlation of the joint DFE was inversely related to genetic differentiation. In humans and D. melanogaster, deleterious mutations had a lower DFE correlation than tolerated mutations, indicating a complex joint DFE. Altogether, the DFE correlation can be reliably inferred, and it offers extensive insight into the genetics of population divergence. 相似文献
128.
129.
130.
Daniela Rusconi Gloria Negri Patrizia Colapietro Chiara Picinelli Donatella Milani Silvia Spena Cinzia Magnani Margherita Cirillo Silengo Lorena Sorasio Vaclava Curtisova Maria Luigia Cavaliere Paolo Prontera Gabriela Stangoni Giovanni Battista Ferrero Elisa Biamino Rita Fischetto Maria Piccione Paolo Gasparini Leonardo Salviati Angelo Selicorni Palma Finelli Lidia Larizza Cristina Gervasini 《Human genetics》2015,134(6):613-626