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Shear stress is an important biomechanical parameter in regulating human mesenchymal stem cell (hMSC) construct development. In this study, the biomechanical characteristics of hMSCs within highly porous 3-D poly (ethylene terephthalate) (PET) matrices in a perfusion bioreactor system were analyzed for two flow rates of 0.1 and 1.5 mL/min, respectively over a 20-day culture period. A 1.4 times higher proliferation rate, higher CFU-F formation, and more fibronectin and HSP-47 secretion at day 20 were observed at the flow rate of 0.1 mL/min compared to those at the flow rate of 1.5 mL/min. The higher flow rate of 1.5 mL/min upregulated osteogenic differentiation potential at day 20 as measured by the expression of alkaline phosphatase activity and calcium deposition in the matrix after 14 days osteogenic induction, consistent with those reported in literatures. Mathematical modeling indicated that shear stress existed in the range of 1 x 10(-5) to 1 x 10(-4) Pa in the constructs up to a depth of 70 microm due to flow penetration in the porous constructs. Analysis of oxygen transport in the constructs for the two flow rates yielded oxygen levels significantly higher than those at which cell growth and metabolism are affected (Jiang et al., 1996). This indicates that differences in convective transport have no significant influence on cell growth and metabolism for the range of flow rates studied. These results demonstrate that shear stress is an important microenvironment parameter that regulates hMSC construct development at a range significantly lower than those reported previously in the perfusion system. 相似文献
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Endostatin,a C-terminal fragment of collagen 18a,inhibits the growth of established tumorsand metastases in vivo by inhibiting angiogenesis.However,the purification procedures required for large-scale production and the attendant cost of these processes,together with the low effectiveness in clinicaltests,suggest that alternative delivery methods might be required for efficient therapeutic use of endostatin.In the present study,we transfected Chinese hamster ovary(CHO)cells with a human endostatin geneexpression vector and encapsulated the CHO cells in alginate-poly-L-lysine microcapsules.The release ofbiologically active endostatin was confirmed using the chicken chorioallantoic membrane assay.The encap-sulated endostatin-expressing CHO cells can inhibit the growth of primary tumors in a subcutaneous B 16tumor model when injected into the abdominal cavity of mouse.These results widen the clinical applicationof the microencapsulated cell endostatin delivery system in cancer treatment. 相似文献
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Food Biophysics - Egg yolk granule is the sedimentary protein fraction of egg yolk. Granules are supramolecular assembly of high-density lipoprotein and phosvitin driven by Ca2+ bridges. Despite... 相似文献
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Chen Zhang Yun Zhu Yugang Liu Xiguang Zhang Qiaoning Yue Li Li Yatang Chen Sheng Lu Zhaowei Teng 《Journal of cellular physiology》2019,234(3):2491-2499
Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair-related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B-AS1 regulating hMSCs osteogenesis. SEMA3B-AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B-AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B-AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix–receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B-AS1 is a target for controlling osteogenesis of hMSCs. 相似文献
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Yu Wang Ye Liu Junwei Li Yi Yang Xiaomeng Ni Haijiao Cheng Teng Huang Yanmei Guo Hongwu Ma Ping Zheng Meng Wang Jibin Sun Yanhe Ma 《Biotechnology and bioengineering》2019,116(11):i-i
CRISPR/Cas9-guided cytidine deaminase enables C:G to T:A base editing in bacterial genome without introduction of lethal double-stranded DNA break, supplement of foreign DNA template, or dependence on inefficient homologous recombination. However, limited by genome-targeting scope, editing window, and base transition capability, the application of base editing in metabolic engineering has not been explored. Herein, four Cas9 variants accepting different protospacer adjacent motif (PAM) sequences were used to increase the genome-targeting scope of bacterial base editing. After a comprehensive evaluation, we demonstrated that PAM requirement of bacterial base editing can be relaxed from NGG to NG using the Cas9 variants, providing 3.9-fold more target loci for gene inactivation in Corynebacterium glutamicum. Truncated or extended guide RNAs were employed to expand the canonical 5-bp editing window to 7-bp. Bacterial adenine base editing was also achieved with Cas9 fused to adenosine deaminase. With these updates, base editing can serve as an enabling tool for fast metabolic engineering. To demonstrate its potential, base editing was used to deregulate feedback inhibition of aspartokinase via amino acid substitution for lysine overproduction. Finally, a user-friendly online tool named gBIG was provided for designing guide RNAs for base editing-mediated inactivation of given genes in any given sequenced genome ( www.ibiodesign.net/gBIG ). 相似文献
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Dapeng Wang Fuqin Bao Yugang Teng Qiang Li 《Bioscience, biotechnology, and biochemistry》2019,83(5):836-844
Osteosarcoma (OS) is the most common malignant bone tumor. In cancer cells, autophagy is related to epithelial-to-mesenchymal transition (EMT). Although microRNA (miR)-506-3p has been demonstrated to act as a tumor suppressor in OS, its role in regulating the EMT process and autophagy remains unknown. The results showed that miR-506-3p directly inhibited the expression of sphingosine kinase 1 (SPHK1) in 143B and SaOS-2 cells. The invasive capability of OS cells was reduced following miR-506-3p mimics transfection, and restored when SPHK1 was overexpressed simultaneously. Further, miR-506-3p mimics initiated mesenchymal-to-epithelial transition (MET) – E-cadherin expression was upregulated, whilst vimentin and fibronectin were downregulated. The basal autophagy flux (LC3II/I) was suppressed by miR-506-3p mimics. The alterations induced by miR-506-3p mimics were partly reversed by SPHK1 overexpression or treatment of rapamycin. Meanwhile, treatment of SPHK1-transfected cells with 3-methyladenine inhibited EMT. The data suggest that miR-506-3p initiates MET and suppresses autophagy in OS cells by targeting SPHK1. 相似文献
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