全文获取类型
收费全文 | 540篇 |
免费 | 58篇 |
专业分类
598篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 10篇 |
2014年 | 19篇 |
2013年 | 29篇 |
2012年 | 23篇 |
2011年 | 28篇 |
2010年 | 17篇 |
2009年 | 15篇 |
2008年 | 30篇 |
2007年 | 14篇 |
2006年 | 21篇 |
2005年 | 12篇 |
2004年 | 15篇 |
2003年 | 13篇 |
2002年 | 11篇 |
2001年 | 16篇 |
2000年 | 11篇 |
1999年 | 18篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 10篇 |
1984年 | 22篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 10篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1971年 | 5篇 |
1969年 | 5篇 |
1959年 | 3篇 |
排序方式: 共有598条查询结果,搜索用时 9 毫秒
81.
Acetylation of rat testis histones H2B and TH2B 总被引:2,自引:1,他引:2
The in vivo acetylation of rat testis histones H3 and H4 has been demonstrated in previous studies. In this study, analysis of purified histone fractions revealed the in vivo acetylation of histone H2B, the testis histone variant designated TH2B, and two or more of the histone H2A variants. These findings are quite significant, because it is possible that all of the core histones are acetylated in elongating spermatids at the time of removal of the entire histone complement for replacement by basic spermatidal transition proteins (S.R. Grimes and N. Henderson, 1983, Arch. Biochem. Biophys. 221, 108-116). 相似文献
82.
Richard S. Jope Ling Song Carol A. Grimes Mary A. Pacheco Ginny E. Dilley Xiaohua Li Herbert Y. Meltzer †James C. Overholser Craig A. Stockmeier 《Journal of neurochemistry》1998,70(2):763-771
Abstract: Comparisons of the activity of the G protein-mediated phosphoinositide signal transduction system and of G protein levels were made in two regions of frontal cortex from eight schizophrenic, alcohol-dependent, and control subjects. G protein-mediated phosphoinositide hydrolysis was measured by stimulating cortical membranes incubated with [3H]phosphatidylinositol with 0.3–10 µM guanosine 5′-O-(3-thio)triphosphate (GTPγS). In frontal cortex areas 8/9, GTPγS-induced phosphoinositide hydrolysis was 50% greater in schizophrenic than control or alcohol-dependent subjects, whereas there were no differences among these groups of subjects in the response to GTPγS in frontal cortex area 10. Agonists for dopaminergic, cholinergic, purinergic, serotonergic, histaminergic, and glutamatergic receptors coupled to the phosphoinositide signaling system increased [3H]phosphatidylinositol hydrolysis in a GTPγS-dependent manner. Responses to most agonists were similar in all three subject groups in both cortical regions, with the largest difference being a 40% greater response to dopaminergic receptor stimulation in frontal cortex 8/9 from schizophrenic subjects. Measurements of the levels of phospholipase C-β, and of α-subunits of Gq, Go, Gi1, Gi2, and Gs, made by immunoblot analyses revealed no differences among the groups of subjects except for increased Gαo in schizophrenic subjects and increased Gαo and Gαi1 in alcohol-dependent subjects. These results demonstrate that schizophrenia is associated with increased activity of the phosphoinositide signal transduction system and increased levels of Gαo, whereas the phosphoinositide system was unaltered in alcohol dependence, but Gαo and Gαi1 were increased. 相似文献
83.
Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex 总被引:13,自引:1,他引:13
Two regions of the genome, a 1-kbp portion of the zeste locus and a 1.1-
kbp portion of the yolk protein 2 locus, were sequenced in six individuals
from each of four species: Drosophila melanogaster, D. simulans, D.
mauritiana, and D. sechellia. The species and strains were the same as
those of a previous study of a 1.9-kbp region of the period locus. No
evidence was found for recent balancing or directional selection or for the
accumulation of selected differences between species. Yolk protein 2 has a
high level of amino acid replacement variation and a low level of
synonymous variation, while zeste has the opposite pattern. This contrast
is consistent with information on gene function and patterns of codon bias.
Polymorphism levels are consistent with a ranking of effective population
sizes, from low to high, in the following order: D. sechellia, D.
melanogaster, D.mauritiana, and D. simulans. The apparent species
relationships are very similar to those suggested by the period locus
study. In particular, D. simulans appears to be a large population that is
still segregating variation that arose before the separation of D.
mauritiana and D. sechellia. It is estimated that the separation of
ancestral D. melanogaster from the other species occurred 2.5-3.4 Mya. The
separations of D. sechellia and D. mauritiana from ancestral D. simulans
appear to have occurred 0.58- 0.86 Mya, with D. mauritiana having diverged
from ancestral D. simulans 0.1 Myr more recently than D. sechellia.
相似文献
84.
Background
Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development. 相似文献85.
Mariana A Antunes Soraia C Abreu Fernanda F Cruz Ana Clara Teixeira Miquéias Lopes-Pacheco Elga Bandeira Priscilla C Olsen Bruno L Diaz Christina M Takyia Isalira PRG Freitas Nazareth N Rocha Vera L Capelozzi Débora G Xisto Daniel J Weiss Marcelo M Morales Patricia RM Rocco 《Respiratory research》2014,15(1)
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. 相似文献
86.
Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes 下载免费PDF全文
Background
Human centromere regions are characterized by the presence of alpha-satellite DNA, replication late in S phase and a heterochromatic appearance. Recent models propose that the centromere is organized into conserved chromatin domains in which chromatin containing CenH3 (centromere-specific H3 variant) at the functional centromere (kinetochore) forms within regions of heterochromatin. To address these models, we assayed formation of heterochromatin and euchromatin on de novo human artificial chromosomes containing alpha-satellite DNA. We also examined the relationship between chromatin composition and replication timing of artificial chromosomes.Results
Heterochromatin factors (histone H3 lysine 9 methylation and HP1α) were enriched on artificial chromosomes estimated to be larger than 3 Mb in size but depleted on those smaller than 3 Mb. All artificial chromosomes assembled markers of euchromatin (histone H3 lysine 4 methylation), which may partly reflect marker-gene expression. Replication timing studies revealed that the replication timing of artificial chromosomes was heterogeneous. Heterochromatin-depleted artificial chromosomes replicated in early S phase whereas heterochromatin-enriched artificial chromosomes replicated in mid to late S phase.Conclusions
Centromere regions on human artificial chromosomes and host chromosomes have similar amounts of CenH3 but exhibit highly varying degrees of heterochromatin, suggesting that only a small amount of heterochromatin may be required for centromere function. The formation of euchromatin on all artificial chromosomes demonstrates that they can provide a chromosome context suitable for gene expression. The earlier replication of the heterochromatin-depleted artificial chromosomes suggests that replication late in S phase is not a requirement for centromere function.87.
Abrescia NG Grimes JM Kivelä HM Assenberg R Sutton GC Butcher SJ Bamford JK Bamford DH Stuart DI 《Molecular cell》2008,31(5):749-761
Recent, primarily structural observations indicate that related viruses, harboring no sequence similarity, infect hosts of different domains of life. One such clade of viruses, defined by common capsid architecture and coat protein fold, is the so-called PRD1-adenovirus lineage. Here we report the structure of the marine lipid-containing bacteriophage PM2 determined by crystallographic analyses of the entire approximately 45 MDa virion and of the outer coat proteins P1 and P2, revealing PM2 to be a primeval member of the PRD1-adenovirus lineage with an icosahedral shell and canonical double beta barrel major coat protein. The view of the lipid bilayer, richly decorated with membrane proteins, constitutes a rare visualization of an in vivo membrane. The viral membrane proteins P3 and P6 are organized into a lattice, suggesting a possible assembly pathway to produce the mature virus. 相似文献
88.
Juliana M Sousa-Canavez Flavio C Canavez Kátia RM Leite Luiz H Camara-Lopes 《Genetic vaccines and therapy》2008,6(1):1-7
Background
Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.Methods
Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.Results
Experiments confirm that electroporation alone is more effective in enhancing reporter gene expression than plasmid injection alone, plasmid conjugation with liposomes followed by injection, or than the combination of liposomes and electroporation. However, with two time courses of multiple electrically-mediated plasmid deliveries, neither the levels nor duration of transgene expression are significantly increased. Tissue damage may increase following a second treatment, no further damage is observed after a third treatment. When electroporation conditions utilized in a mouse model are tested in thicker rat skin, only higher field strengths or longer pulses were as effective in plasmid delivery.Conclusion
Electroporation enhances reporter plasmid delivery to the skin to a greater extent than the liposome conjugation method tested. Multiple deliveries do not necessarily result in higher or longer term expression. In addition, some impact on tissue integrity with respect to surface damage is observed. Pulsing conditions should be optimized for the model and for the expression profile desired. 相似文献89.