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991.
Anqi Qiu Kenichi Oishi Michael I. Miller Constantine G. Lyketsos Susumu Mori Marilyn Albert 《PloS one》2010,5(3)
Background
White matter disruption has been suggested as one of anatomical features associated with Alzheimer''s disease (AD). Diffusion tensor imaging (DTI), which has been widely used in AD studies, obtains new insights into the white matter structure.Methods
We introduced surface-based geometric models of the deep white matter tracts extracted from DTI, allowing the characterization of their shape variations relative to an atlas as well as fractional anisotropy (FA) variations on the atlas surface through large deformation diffeomorphic metric mapping (LDDMM). We applied it to assess local shapes and FA variations of twenty-three deep white matter tracts in 13 patients with AD and 19 healthy control subjects.Results
Our results showed regionally-specific shape abnormalities and FA reduction in the cingulum tract and the sagittal stratum tract in AD, suggesting that disruption in the white matter tracts near the temporal lobe may represent the secondary consequence of the medial temporal lobe pathology in AD. Moreover, the regionally-specific patterns of FA and shape of the white matter tracts were shown to be of sufficient sensitivity to robustly differentiate patients with AD from healthy comparison controls when compared with the mean FA and volumes within the regions of the white matter tracts. Finally, greater FA or deformation abnormalities of the white matter tracts were associated with lower MMSE scores.Conclusion
The regionally-specific shape and FA patterns could be potential imaging markers for differentiating AD from normal aging. 相似文献992.
Kohji Mori Shiho Gotoh Tomoko Yamashita Ryota Uozumi Yuya Kawabe Shinji Tagami Frits Kamp Brigitte Nuscher Dieter Edbauer Christian Haass Yoshitaka Nagai Manabu Ikeda 《The Journal of biological chemistry》2021,297(4)
GGGGCC (G4C2) repeat expansion in the C9orf72 gene has been shown to cause frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Dipeptide repeat proteins produced through repeat-associated non-AUG (RAN) translation are recognized as potential drivers for neurodegeneration. Therefore, selective inhibition of RAN translation could be a therapeutic avenue to treat these neurodegenerative diseases. It was previously known that the porphyrin TMPyP4 binds to G4C2 repeat RNA. However, the consequences of this interaction have not been well characterized. Here, we confirmed that TMPyP4 inhibits C9orf72 G4C2 repeat translation in cellular and in in vitro translation systems. An artificial insertion of an AUG codon failed to cancel the translation inhibition, suggesting that TMPyP4 acts downstream of non-AUG translation initiation. Polysome profiling assays also revealed polysome retention on G4C2 repeat RNA, along with inhibition of translation, indicating that elongating ribosomes stall on G4C2 repeat RNA. Urea-resistant interaction between G4C2 repeat RNA and TMPyP4 likely contributes to this ribosome stalling and thus to selective inhibition of RAN translation. Taken together, our data reveal a novel mode of action of TMPyP4 as an inhibitor of G4C2 repeat translation elongation. 相似文献
993.
Hidenori Kamiguchi Mika Murabayashi Ikuo Mori Akira Horinouchi Kazutaka Higaki 《Biomarkers》2017,22(2):178-188
Context: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable.
Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.
Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.
Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.
Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis. 相似文献
994.
995.
Takuya Ikenari Tatsuya Kawaguchi Rei Ota Miki Matsui Ryota Yoshida Tetsuji Mori 《The journal of histochemistry and cytochemistry》2021,69(9):597
Fluoro-Jade C (FJC) staining has been used to detect degenerating neurons in tissue sections. It is a simple and easy staining procedure and does not depend on the manner of cell death. In some experiments, double staining with FJC and fluorescent immunostaining (FI) is required to identify cell types. However, pretreatment for FJC staining contains some processes that are harsh to fluorophores, and the FI signal is greatly reduced. To overcome this issue, we improved the double staining protocol to acquire clear double-stained images by introducing the labeled streptavidin–biotin system. In addition, several studies indicate that FJC can label non-degenerating glial cells, including resting/reactive astrocytes and activated microglia. Moreover, our previous study indicated that degenerating mesenchymal cells were also labeled by FJC, but it is still unclear whether FJC can label degenerating glial cells. Acute encephalopathy model mice contained damaged astrocytes with clasmatodendrosis, and 6-aminonicotinamide-injected mice contained necrotic astrocytes and oligodendrocytes. Using our improved double staining protocol with FJC and FI, we detected FJC-labeled degenerating astrocytes and oligodendrocytes with pyknotic nuclei. These results indicate that FJC is not specific to degenerating neurons in some experimental conditions: 相似文献
996.
The nematode-trapping fungusArthrobotrys ellipsospora developed an adhesive knob and trapped nematodes when cultured on a low-nutrient medium. It also trapped polystyrene beads
in the same way. The adhesive knob produced mucus that was stained with alcian blue, while mycelium of the fungus was stained
with periodic acid/Schiff (PAS). The amount of mucus increased with in days after culturing in the low-nutrient media. The
fungus completely lost its ability to trap nematodes when treated with EDTA and EGTA, but it recovered the ability after incubation
in the presence of a low concentration of Ca (10−6–10−7 M) for 1 h. Calmodulin inhibitor W-7 also inhibited the trapping ability of the fungus, and there was a significant (p<0.05)
difference between the effects of W-7 and W-5. Ca-binding protein was also detected in the fungus. 相似文献
997.
Apoptotic neurodegeneration induced by influenza A virus infection in the mouse brain 总被引:2,自引:0,他引:2
Neurodegeneration in the brain induced by the WSN strain of influenza A virus was investigated after stereotaxic introduction into the olfactory bulb of C57BL/6 mice. Immunohistochemistry detected WSN virus-infected neurons in the anterior olfactory nucleus as early as day 3 postinfection. Thereafter, they became shrunken and showed loss of neurite-immunolabeling and chromatin condensation. Infected neurons died by day 12, degenerating into multiple small granular bodies. The terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling method demonstrated DNA fragmentation in infected neurons at day 7 and also in such granular bodies at day 12. In perforin-deficient mice, the appearance of virally induced apoptotic neurodegeneration was delayed and virus infection continued for a longer period of 35 days postinfection. These findings indicate that perforin-mediated neuroapoptosis appears significant in exterminating the intracellular pathogen at an early stage of infection. 相似文献
998.
M. Fujisawa T. Udono E. Nogami M. Hirosawa N. Morimura A. Saito M. Seres M. Teramoto K. Nagano Y. Mori H. Uesaka K. Nasu M. Tomonaga G. Idani S. Hirata T. Tsuruyama K. Matsubayashi 《Journal of medical primatology》2014,43(2):111-114
Oral malignancy is rare in chimpanzees. A 34‐year‐old female chimpanzee (Pan troglodytes) at Kumamoto Sanctuary, Japan, had developed it. Treatment is technically difficult for chimpanzees while malignant neoplasm is seemingly rising in captive populations. Widespread expert discussion, guidelines for treatment, especially for great apes in terminal stages is urgently needed. 相似文献
999.
1000.
Asami Y Oishi J Kitazaki H Kamimoto J Kang JH Niidome T Mori T Katayama Y 《Analytical biochemistry》2011,(1):1628-49
Here we developed a simple set-and-mix assay to perform high-throughput screening of protein kinase A (PKA) inhibitors from the LOPAC 1280 compound library. This assay is based on the color change of gold nanoparticles on aggregation induced by a cationic substrate peptide as coagulant. In spite of the simplicity of this assay system, this assay can be applied to drug screening based on cellular kinases. We successfully found several highly active inhibitors, including compounds that have not been reported before. 相似文献