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Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse
Watanabe Y Kokubo H Miyagawa-Tomita S Endo M Igarashi K Aisaki Ki Kanno J Saga Y 《Development (Cambridge, England)》2006,133(9):1625-1634
Notch signaling is implicated in many developmental processes. In our current study, we have employed a transgenic strategy to investigate the role of Notch signaling during cardiac development in the mouse. Cre recombinase-mediated Notch1 (NICD1) activation in the mesodermal cell lineage leads to abnormal heart morphogenesis, which is characterized by deformities of the ventricles and atrioventricular (AV) canal. The major defects observed include impaired ventricular myocardial differentiation, the ectopic appearance of cell masses in the AV cushion, the right-shifted interventricular septum (IVS) and impaired myocardium of the AV canal. However, the fates of the endocardium and myocardium were not disrupted in NICD1-activated hearts. One of the Notch target genes, Hesr1, was found to be strongly induced in both the ventricle and the AV canal of NICD1-activated hearts. However, a knockout of the Hesr1 gene from NICD-activated hearts rescues only the abnormality of the AV myocardium. We searched for additional possible targets of NICD1 activation by GeneChip analysis and found that Wnt2, Bmp6, jagged 1 and Tnni2 are strongly upregulated in NICD1-activated hearts, and that the activation of these genes was also observed in the absence of Hesr1. Our present study thus indicates that the Notch1 signaling pathway plays a suppressive role both in AV myocardial differentiation and the maturation of the ventricular myocardium. 相似文献
83.
In viral infections the host innate immune system is meant to act as a first line defense to prevent viral invasion or replication before more specific protection by the adaptive immune system is generated. In the innate immune response, pattern recognition receptors (PRRs) are engaged to detect specific viral components such as viral RNA or DNA or viral intermediate products and to induce type I interferons (IFNs) and other pro-inflammatory cytokines in the infected cells and other immune cells. Recently these innate immune receptors and their unique downstream pathways have been identified. Here, we summarize their roles in the innate immune response to virus infection, discrimination between self and viral nucleic acids and inhibition by virulent factors and provide some recent advances in the coordination between innate and adaptive immune activation. 相似文献
84.
Raj Kumar Koiri Surendra Kumar Trigun Santosh Kumar Dubey Santosh Singh Lallan Mishra 《Biometals》2008,21(2):117-126
Metal complex–protein interaction is an evolving concept for determining cellular targets of metallodrugs. Lacatate dehydrogenase
(LDH) is critically implicated in tumor growth and therefore, considered to be an important target protein for anti-tumor
metal complexes. Due to efficient biocompatibility of copper (Cu2+) and zinc (Zn2+), we synthesized CubpyAc2 · H2O (Cu-bpy) and ZnbpyAc2 · H2O (Zn-bpy; where bpy = 2,2′ bipyridine, Ac = CH3COO−) complexes and evaluated their interaction with and modulation of LDH in mouse tissues. The increasing concentration of both
the complexes showed a significant shift in UV–Vis spectra of LDH. The binding constant data (Kc = 1 × 103 M−1 for Cu-bpy and 7 × 106 M−1 for Zn-bpy) suggested that Zn-bpy-LDH interaction is stronger than that of Cu-bpy-LDH. LDH modulating potential of the complexes
were monitored by perfusing the mice tissues with non-toxic doses of Cu-bpy and Zn-bpy followed by activity measurement and
analysis of LDH isozymes on non-denaturing polyacrylamide gel electrophoresis (PAGE). As compared to the control sets, Cu-bpy
caused a significant decline (P < 0.05–0.001) in the activity of LDH in all the tissues studied. However, Zn-bpy showed inhibition of LDH only in liver (P < 0.01), kidney (P < 0.001) and heart (P < 0.01), but with no effect in spleen, brain and skeletal muscle tissues. PAGE analysis suggested that all the five LDH isozymes
are equally sensitive to both the complexes in the respective tissues. The results suggest that Cu- and Zn-bpy are able to
interact with and inhibit LDH, a tumor growth supportive target protein at tissue level. 相似文献
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Takumi Chinen Kaho Yamazaki Kaho Hashimoto Ken Fujii Koki Watanabe Yutaka Takeda Shohei Yamamoto Yuka Nozaki Yuki Tsuchiya Daisuke Takao Daiju Kitagawa 《The Journal of cell biology》2021,220(2)
The pericentriolar material (PCM) that accumulates around the centriole expands during mitosis and nucleates microtubules. Here, we show the cooperative roles of the centriole and PCM scaffold proteins, pericentrin and CDK5RAP2, in the recruitment of CEP192 to spindle poles during mitosis. Systematic depletion of PCM proteins revealed that CEP192, but not pericentrin and/or CDK5RAP2, was crucial for bipolar spindle assembly in HeLa, RPE1, and A549 cells with centrioles. Upon double depletion of pericentrin and CDK5RAP2, CEP192 that remained at centriole walls was sufficient for bipolar spindle formation. In contrast, through centriole removal, we found that pericentrin and CDK5RAP2 recruited CEP192 at the acentriolar spindle pole and facilitated bipolar spindle formation in mitotic cells with one centrosome. Furthermore, the perturbation of PLK1, a critical kinase for PCM assembly, efficiently suppressed bipolar spindle formation in mitotic cells with one centrosome. Overall, these data suggest that the centriole and PCM scaffold proteins cooperatively recruit CEP192 to spindle poles and facilitate bipolar spindle formation. 相似文献
87.
Two distinct visual motion mechanisms for smooth pursuit: evidence from individual differences 总被引:1,自引:0,他引:1
Smooth-pursuit eye velocity to a moving target is more accurate after an initial catch-up saccade than before, an enhancement that is poorly understood. We present an individual-differences-based method for identifying mechanisms underlying a physiological response and use it to test whether visual motion signals driving pursuit differ pre- and postsaccade. Correlating moment-to-moment measurements of pursuit over time with two psychophysical measures of speed estimation during fixation, we find two independent associations across individuals. Presaccadic pursuit acceleration is predicted by the precision of low-level (motion-energy-based) speed estimation, and postsaccadic pursuit precision is predicted by the precision of high-level (position-tracking) speed estimation. These results provide evidence that a low-level motion signal influences presaccadic acceleration and an independent high-level motion signal influences postsaccadic precision, thus presenting a plausible mechanism for postsaccadic enhancement of pursuit. 相似文献
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