全文获取类型
收费全文 | 1324篇 |
免费 | 216篇 |
国内免费 | 34篇 |
出版年
2021年 | 34篇 |
2020年 | 14篇 |
2019年 | 16篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 23篇 |
2015年 | 42篇 |
2014年 | 51篇 |
2013年 | 52篇 |
2012年 | 73篇 |
2011年 | 64篇 |
2010年 | 54篇 |
2009年 | 46篇 |
2008年 | 72篇 |
2007年 | 62篇 |
2006年 | 50篇 |
2005年 | 61篇 |
2004年 | 45篇 |
2003年 | 29篇 |
2002年 | 42篇 |
2001年 | 36篇 |
2000年 | 35篇 |
1999年 | 29篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 14篇 |
1994年 | 14篇 |
1992年 | 34篇 |
1991年 | 27篇 |
1990年 | 35篇 |
1989年 | 20篇 |
1988年 | 18篇 |
1987年 | 14篇 |
1986年 | 18篇 |
1985年 | 16篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 15篇 |
1980年 | 12篇 |
1979年 | 16篇 |
1978年 | 15篇 |
1974年 | 19篇 |
1973年 | 21篇 |
1972年 | 17篇 |
1971年 | 16篇 |
1970年 | 20篇 |
1969年 | 24篇 |
1968年 | 16篇 |
1967年 | 15篇 |
1966年 | 17篇 |
排序方式: 共有1574条查询结果,搜索用时 406 毫秒
161.
Moores CA Perderiset M Kappeler C Kain S Drummond D Perkins SJ Chelly J Cross R Houdusse A Francis F 《The EMBO journal》2006,25(19):4448-4457
Doublecortin is a neuronal microtubule-stabilising protein, mutations of which cause mental retardation and epilepsy in humans. How doublecortin influences microtubule dynamics, and thereby brain development, is unclear. We show here by video microscopy that purified doublecortin has no effect on the growth rate of microtubules. However, it is a potent anti-catastrophe factor that stabilises microtubules by linking adjacent protofilaments and counteracting their outward bending in depolymerising microtubules. We show that doublecortin-stabilised microtubules are substrates for kinesin translocase motors and for depolymerase kinesins. In addition, doublecortin does not itself oligomerise and does not bind to tubulin heterodimers but does nucleate microtubules. In cells, doublecortin is enriched at the distal ends of neuronal processes and our data raise the possibility that the function of doublecortin in neurons is to drive assembly and stabilisation of non-centrosomal microtubules in these doublecortin-enriched distal zones. These distinct properties combine to give doublecortin a unique function in microtubule regulation, a role that cannot be compensated for by other microtubule-stabilising proteins and nucleating factors. 相似文献
162.
Dynamical properties of model gene networks and implications for the inverse problem 总被引:1,自引:0,他引:1
We study the inverse problem, or the "reverse-engineering" problem, for two abstract models of gene expression dynamics, discrete-time Boolean networks and continuous-time switching networks. Formally, the inverse problem is similar for both types of networks. For each gene, its regulators and its Boolean dynamics function must be identified. However, differences in the dynamical properties of these two types of networks affect the amount of data that is necessary for solving the inverse problem. We derive estimates for the average amounts of time series data required to solve the inverse problem for randomly generated Boolean and continuous-time switching networks. We also derive a lower bound on the amount of data needed that holds for both types of networks. We find that the amount of data required is logarithmic in the number of genes for Boolean networks, matching the general lower bound and previous theory, but are superlinear in the number of genes for continuous-time switching networks. We also find that the amount of data needed scales as 2(K), where K is the number of regulators per gene, rather than 2(2K), as previous theory suggests. 相似文献
163.
Immunocontraceptive effects on female rabbits infected with recombinant myxoma virus expressing rabbit ZP2 or ZP3 总被引:2,自引:0,他引:2
Mackenzie SM McLaughlin EA Perkins HD French N Sutherland T Jackson RJ Inglis B Müller WJ van Leeuwen BH Robinson AJ Kerr PJ 《Biology of reproduction》2006,74(3):511-521
Recombinant myxoma viruses expressing rabbit zona pellucida 2 (rZP2) or rabbit zona pellucida 3 (rZP3) glycoproteins were constructed and tested in domestic rabbits to assess their potential to induce autoimmune infertility. The recombinant virus expressing rZP2 had no effect on fertility or ovarian histology, despite all animals developing antibodies against the rZP2 antigen. However, recombinant viruses expressing rZP3 induced infertility in 70% of animals at the first breeding. Serum antibodies were relatively short-lived, but antibody was bound to zona pellucida of all rabbits from Day 10 onward. There was no obvious correlation between infertility and rZP3 antibody titer. There was a transient inflammatory response in the ovaries of rZP3-immunized rabbits at Day 15 but no T-cell response to rZP3 could be detected at any time. Dysfunctional follicular formation was present in ovaries from rabbits infected with rZP3-expressing viruses 15-40 days postinfection but this had disappeared at later time points. A recombinant myxoma virus expressing a modified rZP3 antigen with the C-terminal hydrophobic putative anchor sequence deleted was also tested. This virus did not induce either infertility or an antibody response against the zona pellucida. Thus, the context of antigen presentation was crucial for an autoimmune response. 相似文献
164.
A Constitutively Expressed, Truncated umuDC Operon Regulates the recA-Dependent DNA Damage Induction of a Gene in Acinetobacter baylyi Strain ADP1 下载免费PDF全文
In response to environmentally caused DNA damage, SOS genes are up-regulated due to RecA-mediated relief of LexA repression. In Escherichia coli, the SOS umuDC operon is required for DNA damage checkpoint functions and for replicating damaged DNA in the error-prone process called SOS mutagenesis. In the model soil bacterium Acinetobacter baylyi strain ADP1, however, the content, regulation, and function of the umuDC operon are unusual. The umuC gene is incomplete, and a remnant of an ISEhe3-like transposase has replaced the middle 57% of the umuC coding region. The umuD open reading frame is intact, but it is 1.5 times the size of other umuD genes and has an extra 5′ region that lacks homology to known umuD genes. Analysis of a umuD::lacZ fusion showed that umuD was expressed at very high levels in both the absence and presence of mitomycin C and that this expression was not affected in a recA-deficient background. The umuD mutation did not affect the growth rate or survival after UV-induced DNA damage. However, the UmuD-like protein found in ADP1 (UmuDAb) was required for induction of an adjacent DNA damage-inducible gene, ddrR. The umuD mutation specifically reduced the DNA damage induction of the RecA-dependent DNA damage-inducible ddrR locus by 83% (from 12.9-fold to 2.3-fold induction), but it did not affect the 33.9-fold induction of benA, an unrelated benzoate degradation gene. These data suggest that the response of the ADP1 umuDC operon to DNA damage is unusual and that UmuDAb specifically regulates the expression of at least one DNA damage-inducible gene. 相似文献
165.
166.
167.
Kovacevic I Hu J Siehoff-Icking A Opitz N Griffin A Perkins AC Munn AL Müller-Esterl W Popp R Fleming I Jungblut B Hoffmeister M Oess S 《The EMBO journal》2012,31(15):3309-3322
F-BAR proteins are multivalent adaptors that link plasma membrane and cytoskeleton and coordinate cellular processes such as membrane protrusion and migration. Yet, little is known about the function of F-BAR proteins in vivo. Here we report, that the F-BAR protein NOSTRIN is necessary for proper vascular development in zebrafish and postnatal retinal angiogenesis in mice. The loss of NOSTRIN impacts on the migration of endothelial tip cells and leads to a reduction of tip cell filopodia number and length. NOSTRIN forms a complex with the GTPase Rac1 and its exchange factor Sos1 and overexpression of NOSTRIN in cells induces Rac1 activation. Furthermore, NOSTRIN is required for fibroblast growth factor 2 dependent activation of Rac1 in primary endothelial cells and the angiogenic response to fibroblast growth factor 2 in the in vivo matrigel plug assay. We propose a novel regulatory circuit, in which NOSTRIN assembles a signalling complex containing FGFR1, Rac1 and Sos1 thereby facilitating the activation of Rac1 in endothelial cells during developmental angiogenesis. 相似文献
168.
Aruna Govindaraju Alper Uzun LaShonda Robertson Mehmet O Atli Abdullah Kaya Einko Topper Elizabeth A Crate James Padbury Andy Perkins Erdogan Memili 《Reproductive biology and endocrinology : RB&E》2012,10(1):1-10
Background
Degenerative effects of critical regulators of reproduction, the kisspeptin peptides, on cellular aspects of sexually immature male gonads are known but similar information on accessory sex glands remain elusive.Methods
Prepubertal laboratory rats were injected kisspeptin-10 at three different dosage concentrations (10 pg, 1 ng and 1 microgram) for a period of continuous 12 days at the rate of two doses per day. Control rats were maintained in parallel. The day following the end of the experimental period, seminal vesicles were removed and processed for light and electron microscopic examination using the standard methods. DNA damage was estimated by DNA ladder assay and DNA fragmentation assay.Results
The results demonstrated cellular degeneration. Epithelial cell height of seminal vesicles decreased significantly at all doses (P < 0.05). Marked decrease in epithelial folds was readily noticeable, while the lumen was dilated. Ultrastructural changes were characterized by dilatation of endoplasmic reticulum and Golgi complex, heterochromatization of nuclei, invagination of nuclear membranes and a decreased number of secretory granules. Percent DNA damage to the seminal vesicle was 19.54 +/- 1.98, 38.06 +/- 2.09 and 58.18 +/- 2.59 at 10 pg, 1 ng and 1 microgram doses respectively.Conclusion
The study reveals that continuous administration of kisspeptin does not lead to an early maturation but instead severe degeneration of sexually immature seminal vesicles. 相似文献169.
170.
Mitochondrial fission in eukaryotes is mediated by protein complexes that encircle and divide mitochondrial tubules. In budding yeast, fission requires the membrane-anchored protein Fis1 and the dynamin-related GTPase Dnm1. Dnm1 is recruited to mitochondria via interactions with the adaptor proteins Caf4 and Mdv1, which bind directly to Fis1. Unlike Mdv1, a function for Caf4 in mitochondrial membrane scission has not been established. In this study, we demonstrate that Caf4 is a bona fide fission adaptor that assembles at sites of mitochondrial division. We also show that fission complexes may contain Caf4 alone or both Caf4 and Mdv1 without compromising fission function. Although there is a correspondence between Caf4 and Mdv1 expression levels and their contribution to fission, the two adaptor proteins are not equivalent. Rather, our functional and phylogenetic analyses indicate that Caf4 mitochondrial fission activity has diverged from that of Mdv1. 相似文献