全文获取类型
收费全文 | 310篇 |
免费 | 47篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 4篇 |
2014年 | 10篇 |
2013年 | 6篇 |
2012年 | 11篇 |
2011年 | 10篇 |
2010年 | 8篇 |
2009年 | 5篇 |
2008年 | 10篇 |
2007年 | 4篇 |
2006年 | 18篇 |
2005年 | 6篇 |
2004年 | 11篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 21篇 |
1998年 | 12篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 23篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1970年 | 2篇 |
排序方式: 共有357条查询结果,搜索用时 46 毫秒
271.
The setae of parasitic Liphyra brassolis butterfly larvae form a flexible armour for resisting attack by their ant hosts (Lycaenidae: Lepidoptera)
下载免费PDF全文
![点击此处可从《Biological journal of the Linnean Society. Linnean Society of London》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Steen T. Dupont Dany S. Zemeitat David J. Lohman Naomi E. Pierce 《Biological journal of the Linnean Society. Linnean Society of London》2016,117(3):607-619
Caterpillars of the lycaenid butterfly, Liphyra brassolis, live inside the nests of arboreal weaver ants, Oecophylla smaragdina, and eat their brood. Observations of mature larvae suggest that they are impervious to relentless ant molestation, yet they lack sclerotized cuticular plates. We document a novel form of integumental defence that imparts protection from ant attack whilst maintaining the flexibility necessary to walk with a hydraulic skeleton. Analysis of the trunk integument and cuticular structures of early and late instars of L. brassolis using light microscopy, scanning electron microscopy, and histology revealed three new setae types (disc, clavate, and lanceolate), as well as three new cuticular structures (pored sockets, cuticular pores, and cuticular domes). The unique cuticle is covered with lanceolate setae, which act as endocuticular struts, and overlapping scale‐like sockets, which form a hard, flexible integument. The imperfect armour of the early‐instar larvae suggests that abundant, putatively secretory pores are likely to be homologous to pore cupola organs (PCOs) found in other lycaenid larvae and thus may exude semiochemicals to allay ant aggression. The importance of these pores presumably wanes as structural (setal) cuticular defenses are reinforced in later instars, when adult ants have been observed attacking caterpillars to no avail. The caterpillar's antennae are unusual and seem to be involved in manipulating ant larvae into the caterpillar's mouth. Behavioural observations indicate that the dexterity of these structures is associated with eating ants (myrmecophagy). 相似文献
272.
E. coli UvrD is an SF1 helicase involved in several DNA metabolic processes. Although a UvrD dimer is needed for helicase activity, a monomer can translocate with 3' to 5' directionality along single-stranded DNA, and this ATP-dependent translocation is likely involved in RecA displacement. In order to understand how the monomeric translocase functions, we have combined fluorescence stopped-flow kinetic methods with recently developed analysis methods to determine the kinetic mechanism, including ATP coupling stoichiometry, for UvrD monomer translocation along ssDNA. Our results suggest that the macroscopic rate of UvrD monomer translocation is not limited by each ATPase cycle but rather by a slow step (pause) in each translocation cycle that occurs after four to five rapid 1 nt translocation steps, with each rapid step coupled to hydrolysis of one ATP. These results suggest a nonuniform stepping mechanism that differs from either a Brownian motor or previous structure-based inchworm mechanisms. 相似文献
273.
Danielle C. Lohman Deniz Aydin Helaina C. Von Bank Robert W. Smith Vanessa Linke Erin Weisenhorn Molly T. McDevitt Paul Hutchins Emily M. Wilkerson Benjamin Wancewicz Jason Russell Matthew S. Stefely Emily T. Beebe Adam Jochem Joshua J. Coon Craig A. Bingman Matteo Dal Peraro David J. Pagliarini 《Molecular cell》2019,73(4):763-774.e10
274.
Alessandro A. Boezio Loren Berry Brian K. Albrecht David Bauer Steven F. Bellon Christiane Bode April Chen Deborah Choquette Isabelle Dussault Satoko Hirai Paula Kaplan-Lefko Jay F. Larrow Min-Hwa Jasmine Lin Julia Lohman Michele H. Potashman Karen Rex Michael Santostefano Kavita Shah Roman Shimanovich Stephanie K. Springer Yohannes Teffera Yajing Yang Yihong Zhang Jean-Christophe Harmange 《Bioorganic & medicinal chemistry letters》2009,19(22):6307-6312
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. We previously showed that O-linked triazolopyridazines can be potent inhibitors of c-Met. Herein, we report the discovery of a related series of N-linked triazolopyridazines which demonstrate nanomolar inhibition of c-Met kinase activity and display improved pharmacodynamic profiles. Specifically, the potent time-dependent inhibition of cytochrome P450 associated with the O-linked triazolopyridazines has been eliminated within this novel series of inhibitors. N-linked triazolopyridazine 24 exhibited favorable pharmacokinetics and displayed potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver PD model. Once-daily oral administration of 24 for 22 days showed significant tumor growth inhibition in an NIH-3T3/TPR-Met xenograft mouse efficacy model. 相似文献
275.
Loss of heterozygosity (LOH) contributes significantly to the inactivation of tumor suppressor genes and may involve a variety of mechanisms. Studying loss of HLA-A2 alleles in human lymphoblastoid cell lines, we previously showed that mitotic recombination and chromosome loss with concomitant duplication of the non-selected chromosome were the most frequent mechanisms of LOH. In the present study we used the HLA system to determine the rate and spectrum of LOH mutations in the EBV transformed lymphoblastoid cell line R83-4915. Spontaneous loss of HLA-A2 in R83-4915 occurred with a rate of 7.9x10-7 which was 5 to 10-times lower compared to the previously observed rate of loss of HLA-A2 in other lymphoblastoid cell lines. Among the HLA-A2 mutants, 27% did not show LOH of additional chromosome 6 markers. Molecular analysis showed that neither large deletion nor gene conversion was the cause for their mutant phenotype. The remaining mutants showed LOH, which was caused by mitotic recombination (40%) and chromosome loss (33%). However, the chromosome loss observed in mutants of R83-4915 was not accompanied by the duplication of the remaining chromosome. Instead 3 out of 5 mutants became polyploid suggesting that different mechanisms exist to compensate for chromosome loss. In conclusion, the rate and types of LOH that can be observed in cell lines obtained from various donors may depend on the genetic make-up or the transformation status of these cells 相似文献
276.
Alexander G. Kozlov Michael M. Cox Timothy M. Lohman 《The Journal of biological chemistry》2010,285(22):17246-17252
The homotetrameric Escherichia coli single-stranded DNA-binding (SSB) protein plays a central role in DNA replication, repair, and recombination. In addition to its essential activity of binding to transiently formed single-stranded (ss) DNA, SSB also binds an array of partner proteins and recruits them to their sites of action using its four intrinsically disordered C-terminal tails. Here we show that the binding of ssDNA to SSB is inhibited by the SSB C-terminal tails, specifically by the last 8 highly acidic amino acids that comprise the binding site for its multiple partner proteins. We examined the energetics of ssDNA binding to short oligodeoxynucleotides and find that at moderate salt concentration, removal of the acidic C-terminal ends increases the intrinsic affinity for ssDNA and enhances the negative cooperativity between ssDNA binding sites, indicating that the C termini exert an inhibitory effect on ssDNA binding. This inhibitory effect decreases as the salt concentration increases. Binding of ssDNA to approximately half of the SSB subunits relieves the inhibitory effect for all of the subunits. The inhibition by the C termini is due primarily to a less favorable entropy change upon ssDNA binding. These observations explain why ssDNA binding to SSB enhances the affinity of SSB for its partner proteins and suggest that the C termini of SSB may interact, at least transiently, with its ssDNA binding sites. This inhibition and its relief by ssDNA binding suggest a mechanism that enhances the ability of SSB to selectively recruit its partner proteins to sites on DNA. 相似文献
277.
I E Mattern F P Olthoff-Smit B L Jacobs-Meijsing B E Enger-Valk P H Pouwels P H Lohman 《Mutation research》1985,148(1-2):35-45
A system has been developed for the analysis of basepair substitutions that are involved in the reversion of a specific missense mutation. The method is based on the ability of restriction enzymes to recognize and cut specific DNA sequences. Wild-type revertants arising from AT----GC transitions, pseudo wild-type revertants arising from AT-transversions and second site revertants can be distinguished. 4 mutagenic agents have been used, 2,6-diaminopurine, MMS, EMS and ENU, which differ in the types of damage they cause in DNA and in the susceptibility of the damage to repair. All 4 mutagens effectively enhanced the reversion of the mutation studied, trpA223, particularly by increasing the fraction of AT----GC transitions. In this system the influence of the muc genes of plasmid pKM101 was investigated. The presence of these genes reduced the fraction of AT----GC transitions and enhanced the fraction of AT-transversions as well as the fraction of second-site mutations. This change in mutation specificity is found irrespective whether mutation induction occurs mainly via SOS repair (MMS, ENU) or via mainly misreplication (2,6-diAP, EMS). These data suggest that the muc genes are involved in the induction of mutations not only during SOS repair, but also during misreplication. The change in mutation specificity may be caused by a change in the selection and insertion of nucleotides by the DNA-polymerising complex, or by interference with the repair of mismatched bases. 相似文献
278.
M Bignami A Vitelli A Di Muccio M Terlizzese A Calcagnile G A Zapponi P H Lohman L den Engelse E Dogliotti 《Mutation research》1988,193(1):43-51
DNA adduct formation and induction of mutations at 2 gene loci, hypoxanthine-guanine-phosphoribosyltransferase (HPRT) and Na,K-ATPase, were determined simultaneously in Chinese hamster ovary (CHO) cells after treatment with 2 ethylating agents, ethylnitrosourea (ENU) or diethyl sulfate (DES). Doses of DES and ENU, which resulted in equal levels of O6-ethylguanine (O6-EtGua) and O4-ethylthymine (O4-EtThy) in the DNA, were found to induce very similar frequencies of 6-thioguanine-resistant (6-TGr) mutants. Formation of these DNA adducts might therefore be correlated with mutations induced at the HPRT locus. When, however, the same analysis was applied to ouabain-resistant (ouar) mutants, it was found that, at similar levels of O6-EtGua and O4-EtThy, DES induced many more ouar mutants than ENU. This result supports the notion that primary DNA lesions other than O6-EtGua and O4-EtThy are involved in the fixation of ENU- and DES-induced mutations at the Na,K-ATPase gene locus. 相似文献
279.
Interindividual human variation in cisplatinum sensitivity, predictable in an in vitro assay? 总被引:2,自引:0,他引:2
Cisplatinum [cis-diamminedichloroplatinum(II)] is one of the most active antitumour agents and its effect is mainly due to the formation of cisplatinum-DNA crosslinks. Formation of cisplatinum-DNA intrastrand crosslinks in nucleated white blood cells of patients was measured, both in (pretreatment) samples exposed in vitro and in cells collected immediately after in vivo exposure to cisplatinum. Large interpatient variations were found. The in vitro results showed a linear correlation with the in vivo data (cc = 0.91). The in vitro measurements of crosslinks may allow prediction of response and avoidance of toxicity in individual patients. 相似文献
280.
UV-induced DNA excision repair in rat fibroblasts during immortalization and terminal differentiation in vitro 总被引:1,自引:0,他引:1
J. Vijg E. Mullaart F. Berends P. H. M. Lohman D. L. Knook 《Experimental cell research》1986,167(2):517-530
UV-induced DNA excision repair was studied as DNA repair synthesis and dimer removal in rat fibroblast cultures, initiated from either dense or sparse inocula of primary cells grown from skin biopsies. During passaging in vitro an initial increase in DNA repair synthesis, determined both autoradiographically as unscheduled DNA synthesis (UDS) and by means of the BrdU photolysis assay as the number and average size of repair patches, was found to be associated with a morphological shift from small spindle-shaped to large pleiomorphic cells observed over the first twenty generations. In cell populations in growth crisis, a situation exclusively associated with thin-inoculum cultures in which the population predominantly consisted of large pleiomorphic cells, UDS was found to occur at a low level. After development of secondary cultures into immortal cell lines, both repair synthesis and morphology appeared to be the same as in the original primary spindle-shaped cells. At all passages the capacity to remove UV-induced pyrimidine dimers was found to be low, as indicated by the persistence of Micrococcus luteus UV endonuclease-sensitive sites. These results are discussed in the context of terminal differentiation and immortalization of rat fibroblasts upon establishment in vitro. 相似文献