全文获取类型
收费全文 | 598篇 |
免费 | 54篇 |
出版年
2023年 | 8篇 |
2022年 | 11篇 |
2021年 | 14篇 |
2020年 | 17篇 |
2019年 | 17篇 |
2018年 | 25篇 |
2017年 | 17篇 |
2016年 | 29篇 |
2015年 | 40篇 |
2014年 | 49篇 |
2013年 | 36篇 |
2012年 | 52篇 |
2011年 | 43篇 |
2010年 | 25篇 |
2009年 | 19篇 |
2008年 | 33篇 |
2007年 | 41篇 |
2006年 | 25篇 |
2005年 | 37篇 |
2004年 | 28篇 |
2003年 | 18篇 |
2002年 | 18篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有652条查询结果,搜索用时 15 毫秒
641.
Maren L. Smith Kristin M. Mignogna Jo L. Rokita Lorna MacLeod M. Imad Damaj Michael F. Miles 《Genes, Brain & Behavior》2023,22(2):e12844
Nicotine is the reinforcing ingredient in tobacco. Following chronic exposure, sudden cessation of nicotine use produces negative symptoms of withdrawal that contribute to dependence. The molecular mechanisms underlying nicotine withdrawal behaviors, however, are poorly understood. Using recombinant inbred mice, chronic nicotine was delivered by minipump and withdrawal induced using mecamylamine. Somatic signs of withdrawal, and anxiety-like behavior using elevated plus maze, were then assessed. Interval mapping was used to identify associations between genetic variation and withdrawal behaviors, and with basal gene expression. Differential gene expression following nicotine exposure and withdrawal was also assessed in progenitor mice using microarrays. Quantitative trait loci mapping identified chromosome intervals with significant genetic associations to somatic signs of withdrawal or withdrawal-induced anxiety-like behavior. Using bioinformatics, and association with basal gene expression in nucleus accumbens, we implicated Rb1, Bnip3l, Pnma2, Itm2b, and Kif13b as candidate genes for somatic signs of withdrawal, and Galr1, which showed trans-regulation from a region of chromosome 14 that was associated with somatic signs of withdrawal. Candidate genes within the chromosome 9 region associated with anxiety-like withdrawal behavior included Dixdc1, Ncam1, and Sorl1. Bioinformatics identified six genes that were also significantly associated with nicotine or alcohol traits in recent human genome-wide association studies. Withdrawal-associated somatic signs and anxiety-like behavior had strong non-overlapping genetic associations, respectively, with regions of chromosome 14 and chromosome 9. Genetic, behavioral and gene expression correlations, and bioinformatics analysis identified several candidate genes that may represent novel molecular targets for modulating nicotine withdrawal symptoms. 相似文献
642.
643.
Maren Klinger Wenbo Wang Stefanie Kuhns Felix B?renz Stefanie Dr?ger-Meurer Gislene Pereira Oliver J. Gruss 《Molecular biology of the cell》2014,25(4):495-507
In differentiated human cells, primary cilia fulfill essential functions in converting mechanical or chemical stimuli into intracellular signals. Formation and maintenance of cilia require multiple functions associated with the centriole-derived basal body, from which axonemal microtubules grow and which assembles a gate to maintain the specific ciliary proteome. Here we characterize the function of a novel centriolar satellite protein, synovial sarcoma X breakpoint–interacting protein 2 (SSX2IP), in the assembly of primary cilia. We show that SSX2IP localizes to the basal body of primary cilia in human and murine ciliated cells. Using small interfering RNA knockdown in human cells, we demonstrate the importance of SSX2IP for efficient recruitment of the ciliopathy-associated satellite protein Cep290 to both satellites and the basal body. Cep290 takes a central role in gating proteins to the ciliary compartment. Consistent with that, loss of SSX2IP drastically reduces entry of the BBSome, which functions to target membrane proteins to primary cilia, and interferes with efficient accumulation of the key regulator of ciliary membrane protein targeting, Rab8. Finally, we show that SSX2IP knockdown limits targeting of the ciliary membrane protein and BBSome cargo, somatostatin receptor 3, and significantly reduces axoneme length. Our data establish SSX2IP as a novel targeting factor for ciliary membrane proteins cooperating with Cep290, the BBSome, and Rab8. 相似文献
644.
Acetazolamide, a potent and highly specific inhibitor of carbonic anhydrase, is teratogenic in mammalian embryos and when administered during early limb development causes unique limb defects in a time- and dose-dependent manner. The regenerating urodele limb is often considered to be a good experimental analog of limb development and, if it employs the same mechanisms of tissue interactions during pattern formation, should be susceptible to teratogens which selectively disrupt developmental limb patterning. This study demonstrates that while carbonic anhydrase inhibition is toxic to the red-backed salamander, Plethodon cinereus, it does not have the same teratogenic effect on limb regeneration as seen in mammalian limb development. Several points are considered as to why the regenerating limb, at least in this salamander species, may not be suitable for studying this class of teratogen. 相似文献
645.
646.
Markus Morawski Alexander Dityatev Maike Hartlage-Rübsamen Maren Blosa Max Holzer Katharina Flach Sanja Pavlica Galina Dityateva Jens Grosche Gert Brückner Melitta Schachner 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1654)
Perineuronal nets (PNs) in the brains of tenascin-R-deficient (tn-r−/−) mice develop in temporal concordance with those of wild-type (tn-r+/+) mice. However, the histological appearance of PNs is abnormal in adult tn-r−/− mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r−/− mice and whether the structure of PNs could be normalized. In tn-r−/− cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r+/+ mice. Experiments to normalize the structure of PNs in tn-r−/− organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r+/+ and tn-r−/− brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin Wisteria floribunda agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction. 相似文献
647.
648.
Chemistry of the renal reabsorption of bicarbonate 总被引:6,自引:0,他引:6
T H Maren 《Canadian journal of physiology and pharmacology》1974,52(6):1041-1050
649.
Aspergillus species are increasingly important human pathogens. It is not known whether toxic metabolites of many of these pathogenic
species can act as virulence factors in aspergillosis. We examined isolates of aflatoxin and ochratoxin-producing species
for toxin production in ex vivo conditions. Seven of the 21 aflatoxin-producing isolates screened produced aflatoxin at 35
and 37°C on the general medium yeast extract sucrose agar (YES). However, none of them produced toxin at these temperatures
on brain heart infusion agar (BHA), a medium that mimics human tissue, or on BHA with modified pH or sugar levels. Six of
the 12 ochratoxin-producing isolates examined produced toxin at 35°C on YES. All three isolates of A. alliaceus produced ochratoxin on BHA or modified BHA at 37°C. One strain of A. pseudoelegans produced a minute amount of ochratoxin on modified BHA at 37°C. These data indicate that aflatoxin is an unlikely virulence,
factor but that ochratoxin may be a potential virulence factor in aspergillosis. 相似文献
650.