全文获取类型
收费全文 | 445篇 |
免费 | 71篇 |
出版年
2021年 | 7篇 |
2020年 | 9篇 |
2018年 | 5篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 16篇 |
2013年 | 12篇 |
2012年 | 15篇 |
2011年 | 11篇 |
2010年 | 9篇 |
2009年 | 18篇 |
2008年 | 19篇 |
2007年 | 19篇 |
2006年 | 18篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 14篇 |
2001年 | 10篇 |
2000年 | 13篇 |
1999年 | 12篇 |
1998年 | 10篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 18篇 |
1990年 | 13篇 |
1989年 | 9篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 15篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1974年 | 7篇 |
1971年 | 3篇 |
1941年 | 3篇 |
1940年 | 5篇 |
1938年 | 3篇 |
1934年 | 4篇 |
1929年 | 3篇 |
1927年 | 4篇 |
排序方式: 共有516条查询结果,搜索用时 171 毫秒
41.
Natural populations of sexually reproducing Drosophila mercatorum are capable of a very low rate of parthenogenesis, but this mode of reproduction has apparently never characterized an entirely asexual population in this species. The high abortion rate observed in laboratory parthenogenetic lines suggests that developmental constraints may cause the failure of this trait to spread in nature. To investigate the basis of this developmental instability and how it may affect the evolution of parthenogenesis in natural populations, early embryonic development was compared between one sexual and four parthenogenetic laboratory strains of D. mercatorum. There is a large amount of variation within a given parthenogenetic strain, suggesting that parthenogenesis is associated with a general breakdown of developmental stability. There is relatively little variation among different parthenogenetic strains, suggesting that most abortions are due to a feature inherent to parthenogenetic reproduction rather than a feature of a particular genome. Likewise, there is little variation between parthenogenetic and sexual strains in the causes of abortions, suggesting that the developmental problems encountered by parthenogenetic lineages are not unique to parthenogens. Thus, the failure of parthenogenesis to spread within D. mercatorum can be attributed to no particular developmental constraint per se operating after the initiation of embryogenesis. However, the overall increase in all developmental problems that occurs with the transition from sexual to parthenogenetic development suggests that the high degree of developmental instability associated with parthenogenesis may be considered a developmental constraint in its own right. 相似文献
42.
Exposure of mesangial cells to ionic Cd(2+) induces the proto-oncogene c-fos, while activating both Erk and stress-activated protein kinase (SAPK) MAP kinase pathways. While we have previously used a pharmacological inhibitor of Erk activation to implicate involvement of this pathway in the induction of c-fos by Cd(2+), the consequences of SAPK activation remained unknown. Here we use dominant negative inhibitors of the SAPK kinases, SEK1 and MKK7, to show that Cd(2+) activates SAPK through MKK7, but that partial inhibition of SAPK alone is insufficient to significantly affect the magnitude of the Cd(2+)-dependent increase in c-fos mRNA. However, inhibition of Erk and SAPK pathways together abrogates the increase, suggesting that these pathways act in concert in the induction of c-fos by this toxic metal. 相似文献
43.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
44.
45.
Zachary S. Templeton Michael H. Bachmann Rajiv V. Alluri William J. Maloney Christopher H. Contag Bonnie L. King 《Journal of visualized experiments : JoVE》2015,(97)
Bone is the most common site of breast cancer metastasis. Although it is widely accepted that the microenvironment influences cancer cell behavior, little is known about breast cancer cell properties and behaviors within the native microenvironment of human bone tissue.We have developed approaches to track, quantify and modulate human breast cancer cells within the microenvironment of cultured human bone tissue fragments isolated from discarded femoral heads following total hip replacement surgeries. Using breast cancer cells engineered for luciferase and enhanced green fluorescent protein (EGFP) expression, we are able to reproducibly quantitate migration and proliferation patterns using bioluminescence imaging (BLI), track cell interactions within the bone fragments using fluorescence microscopy, and evaluate breast cells after colonization with flow cytometry. The key advantages of this model include: 1) a native, architecturally intact tissue microenvironment that includes relevant human cell types, and 2) direct access to the microenvironment, which facilitates rapid quantitative and qualitative monitoring and perturbation of breast and bone cell properties, behaviors and interactions. A primary limitation, at present, is the finite viability of the tissue fragments, which confines the window of study to short-term culture. Applications of the model system include studying the basic biology of breast cancer and other bone-seeking malignancies within the metastatic niche, and developing therapeutic strategies to effectively target breast cancer cells in bone tissues. 相似文献
46.
47.
Olson MM Templeton LJ Suh W Youderian P Sariaslani FS Gatenby AA Van Dyk TK 《Applied microbiology and biotechnology》2007,74(5):1031-1040
Escherichia coli K12 strains producing l-phenylalanine were converted to l-tyrosine-producing strains using a novel genetic method for gene replacement. We deleted a region of the E. coli K12 chromosome including the pheA gene encoding chorismate mutase/prephenate dehydratase, its leader peptide (pheL), and its promoter using a new polymerase chain reaction-based method that does not leave a chromosomal scar. For high level
expression of tyrA, encoding chorismate mutase/prephenate dehydrogenase, its native promoter was replaced with the strong trc promoter. The linked ΔpheLA and Ptrc-tyrA::KanR genetic modifications were moved into l-phenylalanine producing strains by generalized transduction to convert l-phenylalanine-producing strains to l-tyrosine-producing strains. Moreover, introduction of a plasmid carrying genes responsible for sucrose degradation into these
strains enabled l-tyrosine-production from sucrose. 相似文献
48.
Templeton TJ 《Trends in parasitology》2007,23(5):205-212
The natural histories of free-living and pathogenic protozoans have been described in over a century of studies, spanning a range of disciplines such as microscopic, cellular, taxonomic, pathological, clinical and molecular. Only in the last decade has this landscape of work benefited from the availability of whole-genome nucleotide sequence data. For many pathogens, it is now possible to overlay analyses of protein repertoires onto the current spectrum of knowledge. This article illuminates protozoan natural histories, particularly the rapidly evolving and highly adaptive direct physical interface of apicomplexan parasites and their hosts, by providing a brief introduction to the origin and phylogenetic distribution of parasite-encoded surface proteins and their component domains. 相似文献
49.
Magda Budzowska Thomas GW Graham Alexandra Sobeck Shou Waga Johannes C Walter 《The EMBO journal》2015,34(14):1971-1985
DNA interstrand cross‐links (ICLs) are repaired in S phase by a complex, multistep mechanism involving translesion DNA polymerases. After replication forks collide with an ICL, the leading strand approaches to within one nucleotide of the ICL (“approach”), a nucleotide is inserted across from the unhooked lesion (“insertion”), and the leading strand is extended beyond the lesion (“extension”). How DNA polymerases bypass the ICL is incompletely understood. Here, we use repair of a site‐specific ICL in Xenopus egg extracts to study the mechanism of lesion bypass. Deep sequencing of ICL repair products showed that the approach and extension steps are largely error‐free. However, a short mutagenic tract is introduced in the vicinity of the lesion, with a maximum mutation frequency of ~1%. Our data further suggest that approach is performed by a replicative polymerase, while extension involves a complex of Rev1 and DNA polymerase ζ. Rev1–pol ζ recruitment requires the Fanconi anemia core complex but not FancI–FancD2. Our results begin to illuminate how lesion bypass is integrated with chromosomal DNA replication to limit ICL repair‐associated mutagenesis. 相似文献