全文获取类型
收费全文 | 11817篇 |
免费 | 915篇 |
国内免费 | 3篇 |
出版年
2023年 | 74篇 |
2022年 | 89篇 |
2021年 | 180篇 |
2020年 | 170篇 |
2019年 | 144篇 |
2018年 | 337篇 |
2017年 | 301篇 |
2016年 | 384篇 |
2015年 | 568篇 |
2014年 | 593篇 |
2013年 | 760篇 |
2012年 | 1039篇 |
2011年 | 1035篇 |
2010年 | 607篇 |
2009年 | 490篇 |
2008年 | 834篇 |
2007年 | 762篇 |
2006年 | 701篇 |
2005年 | 669篇 |
2004年 | 637篇 |
2003年 | 533篇 |
2002年 | 473篇 |
2001年 | 152篇 |
2000年 | 131篇 |
1999年 | 102篇 |
1998年 | 76篇 |
1997年 | 66篇 |
1996年 | 69篇 |
1995年 | 59篇 |
1994年 | 40篇 |
1993年 | 55篇 |
1992年 | 53篇 |
1991年 | 34篇 |
1990年 | 43篇 |
1989年 | 28篇 |
1988年 | 20篇 |
1987年 | 26篇 |
1986年 | 27篇 |
1985年 | 32篇 |
1984年 | 25篇 |
1983年 | 31篇 |
1982年 | 30篇 |
1981年 | 19篇 |
1980年 | 17篇 |
1979年 | 28篇 |
1978年 | 30篇 |
1977年 | 15篇 |
1976年 | 22篇 |
1975年 | 24篇 |
1973年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 156 毫秒
991.
Bérard J Kalbe C Lösel D Tuchscherer A Rehfeldt C 《Histochemistry and cell biology》2011,136(2):217-225
In pigs, myogenesis is a biphasic phenomenon with the formation of primary and secondary fibres. Hyperplasia was reported
to be accomplished around 90 days of gestation. However, some studies suggest a substantial increase in the total fibre number
(TFN) from birth to weaning by counting fibre number in the muscle cross sections. The aim of this study was to establish
in which way TFN increases after birth and whether this increase is imputable to new (tertiary) myofibres and/or fibre elongation.
The semitendinosus muscle of 128 piglets was examined at days 1 (n = 63), 7 (n = 12), 21 (n = 12), and 28 (n = 41) of age. TFN was increased at days 7, 21 and 28 of age when compared with day 1 (P < 0.01). From day 1 to 28, TFN increased from 463 × 103 to 825 × 103. Microscopy of longitudinal and transversal serial sections revealed that at day 7 of age very small fibres expressing the
embryonic myosin heavy chain (MyHC) isoform were apparent all over the muscle. In addition, intrafascicular terminations of
normal-sized fibres expressed the embryonic MyHC isoform. These data suggest that the TFN in the pig muscle is not fixed at
birth and its postnatal increase may be related to both elongation of existing muscle fibres and genesis of tertiary myofibres,
mainly between birth and 3 weeks of age. 相似文献
992.
Widdick DA Hicks MG Thompson BJ Tschumi A Chandra G Sutcliffe IC Brülle JK Sander P Palmer T Hutchings MI 《Molecular microbiology》2011,80(5):1395-1412
Following translocation, bacterial lipoproteins are lipidated by lipoprotein diacylglycerol transferase (Lgt) and cleaved of their signal peptides by lipoprotein signal peptidase (Lsp). In Gram-negative bacteria and mycobacteria, lipoproteins are further lipidated by lipoprotein N-acyl transferase (Lnt), to give triacylated lipoproteins. Streptomyces are unusual amongst Gram-positive bacteria because they export large numbers of lipoproteins via the twin arginine protein transport (Tat) pathway. Furthermore, some Streptomyces species encode two Lgt homologues and all Streptomyces species encode two homologues of Lnt. Here we characterize lipoprotein biogenesis in the plant pathogen Streptomyces scabies and report that lgt and lsp mutants are defective in growth and development while only moderately affected in virulence. Lipoproteins are lost from the membrane in an S. scabies lgt mutant but restored by expression of Streptomyces coelicolor lgt1 or lgt2 confirming that both encode functional Lgt enzymes. Furthermore, lipoproteins are N-acylated in Streptomyces with efficient N-acylation dependent on Lnt1 and Lnt2. However, deletion of lnt1 and lnt2 has no effect on growth, development or virulence. We thus present a detailed study of lipoprotein biogenesis in Streptomyces, the first study of Lnt function in a monoderm bacterium and the first study of bacterial lipoproteins as virulence factors in a plant pathogen. 相似文献
993.
Graveline R Mourez M Hancock MA Martin C Boisclair S Harel J 《Molecular microbiology》2011,81(5):1286-1299
F165(1) and the pyelonephritis-associated pili (Pap) are two members of the type P family of adhesive factors that play a key role in the establishment of disease caused by extraintestinal Escherichia coli (ExPEC) strains. They are both under the control of an epigenetic and reversible switch that defines the number of fimbriated (ON) and afimbriated (OFF) cells within a clonal population. Our present study demonstrates that the high level of ON cells found during F165(1) phase variation is due to altered stability of the DNA complex formed by the leucine-responsive regulatory protein (Lrp) at its repressor binding sites 1-3; after each cell cycle, complex formation is also modulated by the local regulator FooI (homologue to PapI) which promotes the transit of Lrp towards its activator binding sites 4-6. Furthermore, we identified two nucleotides (T490, G508) surrounding the Lrp binding site 1 that are critical to maintaining a high OFF to ON switch rate during F165(1) phase variation, as well as switching Pap fimbriae towards the OFF state. 相似文献
994.
Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance 总被引:1,自引:0,他引:1
Michèle Balage Joëlle DupontIsabelle Mothe-Satney Sophie TesseraudLaurent Mosoni Dominique Dardevet 《The Journal of nutritional biochemistry》2011,22(3):219-226
Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucine supplementation on insulin signaling and sensitivity in 4-month old rats fed a 15% protein diet supplemented (LEU) or not (C) with 4.5% leucine. An oral glucose tolerance test was performed in each rat at the end of the supplementation and glucose transport was measured in vitro using isolated epitrochlearis muscles incubated with 2-deoxy-d-[3H]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IRβ, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (−36%, −36% and −38% respectively, P<.05) whereas S6K1, S6rp and 4EBP1 phosphorylations were similar. Overall glucose tolerance was reduced in leucine-supplemented rats and was associated with accumulation of perirenal adipose tissue (+27%, P<.05). Conversely, in vitro insulin-response of muscle glucose transport tended to be improved in leucine-supplemented rats. In conclusion, dietary leucine supplementation in adult rats induced a delay in the postprandial stimulation in the early steps of muscle insulin signaling without muscle resistance on insulin-induced glucose uptake. However, it resulted in overall glucose intolerance linked to increased local adiposity. Further investigations are necessary to clearly define the beneficial and/or deleterious effects of chronic dietary leucine supplementation in healthy subjects. 相似文献
995.
Connectivity is critical to the maintenance of biodiversity in fragmented landscapes, but its effects differ depending on the arrangement of linkages within a habitat network. Additionally, heterogeneity in habitat quality within the habitat network can alter patterns of diversity at local and regional scales in the metacommunity. Using a controlled experiment we examined the interactive effects of habitat connectivity, network form (linear vs square), and habitat patch quality on a moss‐inhabiting microarthropod community. We fragmented moss habitat while controlling for habitat loss, and altered habitat patch quality by regulating moisture conditions in landscapes differing in patch arrangement. Habitat patch quality had a significant effect on patterns of species richness, extinction, abundance and biomass. The effects of network form on diversity were strongest in heterogeneous landscapes. Gamma and beta diversity were greatest in continuous and linear landscapes. However, linear habitat networks showed marked patch specific edge effects that were detrimental to diversity under heterogeneous conditions. We provide direct evidence that habitat network structure impacts species community properties through mass effects, that are most evident when heterogeneity in habitat patch quality is present within the network. We conclude that habitat quality at the individual patch level and the distribution of high‐quality habitat within the network are important factors affecting biodiversity in metacommunities. 相似文献
996.
TRP channels have emerged as key biological sensors in vision, taste, olfaction, hearing, and touch. Despite their importance, virtually nothing is known about the folding and transport of TRP channels during biosynthesis. Here, we identify XPORT (exit protein of rhodopsin and TRP) as a critical chaperone for TRP and its G protein-coupled receptor (GPCR), rhodopsin (Rh1). XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90. XPORT promotes the targeting of TRP to the membrane in Drosophila S2 cells, a finding that provides a critical first step toward solving a longstanding problem in?the successful heterologous expression of TRP. Mutations in xport result in defective transport of TRP and Rh1, leading to retinal degeneration. Our results identify XPORT as a molecular chaperone and provide a mechanistic link between TRP channels and their GPCRs during biosynthesis and transport. 相似文献
997.
Assreuy AM Pinto NV Lima Mota MR Passos Meireles AV Cajazeiras JB Nobre CB Soares PM Cavada BS 《Protein and peptide letters》2011,18(11):1107-1111
The vasorelaxant effect of the lectin of Pisum arvense (PAL) seeds was investigated in rat aorta. PAL (10-100 μg/ml) was applied on aorta rings, with or without endothelium, pre-contracted with phenylephrine (Phe; 0.1 μM). Participation of endothelium derived relaxant factors was evaluated incubating the tissue with indomethacin (10 μM), L-nitro arginine methyl ester (L-NAME, 100 μM) and tetraethylammonium (TEA, 5 mM) before addition of PAL. The role of the lectin domain was investigated by addition of PAL into tissue in presence of glucose (3x 10?? M), or N-acetyl Dglucosamine (GlcNAc; 3 x 10?? M). The importance of extracellular calcium (Ca2?e) or interaction with muscarinic receptors in the relaxant effect was evaluated by addition of PAL into aorta rings containing calcium free solution (OCa) and atropine (1 μ M), respectively. PAL induced concentration-dependent relaxation in endothelized aorta (IC50 =58.38 ± 1.87 μg/ml), which was reversed by L-NAME and glucose. The lectin effect was totally inhibited when the preparation was inserted in OCa, but not in presence of atropine. Summarizing, our data showed a relaxant effect of PAL in isolated rat aorta rings in presence of endothelium, suggestive of interaction between the lectin carbohydrate binding sites with specific receptors located in vascular endothelial cells leading to nitric oxide synthase activation. This effect seems to require Ca2?e but is independent on muscarinic receptors interaction. 相似文献
998.
999.
Chételat G 《Médecine sciences : M/S》2011,27(2):193-198
Neuroimaging offers a promising tool for the priority goals of current researches in Alzheimer's disease (AD) including early diagnosis, monitoring the progression of the disease and understanding the underlying mechanisms. The brain profiles of atrophy and hypometabolism associated with AD are well known and they can be used as support for early diagnosis, although the accuracy of each of these biomarkers on its own is not sufficient. An increasing number of studies highlights the relevance of disconnection processes in the development and progression of AD. The recent development of PET tracers such as the Pittsburg compound (PiB) allowing to visualize in vivo one of the neuropathological lesions characterizing AD (i.e. beta-amyloid depositions) offers a unique opportunity to better understand the mechanisms underlying this multifaceted disease. 相似文献
1000.