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991.
992.
Benjamin Lehne Alexander W Drong Marie Loh Weihua Zhang William R Scott Sian-Tsung Tan Uzma Afzal James Scott Marjo-Riitta Jarvelin Paul Elliott Mark I McCarthy Jaspal S Kooner John C Chambers 《Genome biology》2015,16(1)
DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification of methylation quantitative trait loci for hypothesis driven follow-up experiments.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0600-x) contains supplementary material, which is available to authorized users. 相似文献993.
Transgenic soya bean seeds accumulating β‐carotene exhibit the collateral enhancements of oleate and protein content traits 下载免费PDF全文
994.
McCarthy P Chattopadhyay M Millhauser GL Tsarevsky NV Bombalski L Matyjaszewski K Shimmin D Avdalovic N Pohl C 《Analytical biochemistry》2007,366(1):1-8
Atom transfer radical polymerization (ATRP) was employed to create isolated, metal-containing nanoparticles on the surface of nonporous polymeric beads with the goal of developing a new immobilized metal affinity chromatography (IMAC) stationary phase for separating prion peptides and proteins. Transmission electron microscopy was used to visualize nanoparticles on the substrate surface. Individual ferritin molecules were also visualized as ferritin-nanoparticle complexes. The column's resolving power was tested by synthesizing peptide analogs to the copper binding region of prion protein and injecting mixtures of these analogs onto the column. As expected, the column was capable of separating prion-related peptides differing in number of octapeptide repeat units (PHGGGWGQ), (PHGGGWGQ)(2), and (PHGGGWGQ)(4). Unexpectedly, the column could also resolve peptides containing the same number of repeats but differing only in the presence of a hydrophilic tail, Q-->A substitution, or amide nitrogen methylation. 相似文献
995.
Sharma R Prasad V McCarthy ET Savin VJ Dileepan KN Stechschulte DJ Lianos E Wiegmann T Sharma M 《Molecular and cellular biochemistry》2007,297(1-2):161-169
Increased infiltration of the kidney by mast cells is associated with proteinuria, and interstitial fibrosis in various renal
diseases. Mast cells produce serine proteases including tryptase and chymase (MCC) that act via protease-activated receptors
(PARs) to induce synthesis of fibrogenic cytokines by renal cells. In the present study, we investigated direct effect of
MCC and role of PARs on glomerular albumin permeability (Palb). Isolated rat glomeruli were incubated with MCC (0.1, 1, 10, and 100 ng/ml) for 5–30 min in presence or absence of PAR-1
and PAR-2 blocking antibodies. Palb was determined from the change in glomerular volume in response to an albumin oncotic gradient. The effect of direct activation
of PARs on Palb was verified by incubating glomeruli with synthetic hexapeptide known to activate PAR-1 and PAR-2. MCC increased Palb of isolated rat glomeruli in a dose- and time-dependent manner. Blocking PAR-2 prevented MCC-mediated increase in Palb. RT-PCR analysis of glomerular RNA demonstrated the presence of constitutively expressed PAR-1, -2, and -3 and low levels
of PAR-4. In addition, direct activation of PAR-2 by hexapeptide SLIGKV increased Palb comparable to MCC, whereas PAR-1 activation by TFLLRN had no effect on Palb. Our results document that MCC induces increase in Palb and that this effect is mediated through PAR-2. MCC may also play a role in renal scarring. We propose that inhibiting MCC
activity or blocking the activation of PAR-2 may provide new targets for therapy in renal diseases. 相似文献
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Background
DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated.Methodology/Principal Findings
We used Dyt1 knock out (Dyt1 KO), Dyt1 ΔGAG knock-in (Dyt1 KI), and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT) or human ΔGAG mutant allele (DYT1 hMT). D1R, D2R, and Gα(olf) protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60) male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14) male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf) protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice.Conclusion/Significance
We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice) produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology. 相似文献999.
Mary K. McCarthy Megan C. Procario Carol A. Wilke Bethany B. Moore Jason B. Weinberg 《PloS one》2015,10(9)
Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs. 相似文献
1000.
Paul C. Wang Albert Mwango Sarah Moberley Benjamin J. Brockman Alison L. Connor Penelope Kalesha-Masumbu Simon Mutembo Maximillian Bweupe Pascalina Chanda-Kapata Godfrey Biemba Davidson H. Hamer Benjamin Chibuye Elizabeth McCarthy 《PloS one》2015,10(10)