全文获取类型
收费全文 | 5667篇 |
免费 | 428篇 |
国内免费 | 367篇 |
专业分类
6462篇 |
出版年
2024年 | 12篇 |
2023年 | 66篇 |
2022年 | 158篇 |
2021年 | 285篇 |
2020年 | 203篇 |
2019年 | 229篇 |
2018年 | 220篇 |
2017年 | 186篇 |
2016年 | 277篇 |
2015年 | 357篇 |
2014年 | 441篇 |
2013年 | 454篇 |
2012年 | 481篇 |
2011年 | 431篇 |
2010年 | 261篇 |
2009年 | 227篇 |
2008年 | 278篇 |
2007年 | 231篇 |
2006年 | 173篇 |
2005年 | 129篇 |
2004年 | 138篇 |
2003年 | 125篇 |
2002年 | 113篇 |
2001年 | 98篇 |
2000年 | 89篇 |
1999年 | 93篇 |
1998年 | 65篇 |
1997年 | 64篇 |
1996年 | 39篇 |
1995年 | 53篇 |
1994年 | 55篇 |
1993年 | 53篇 |
1992年 | 67篇 |
1991年 | 48篇 |
1990年 | 34篇 |
1989年 | 29篇 |
1988年 | 28篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 22篇 |
1984年 | 12篇 |
1983年 | 11篇 |
1982年 | 11篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 18篇 |
1978年 | 8篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有6462条查询结果,搜索用时 15 毫秒
51.
52.
53.
Stéphane Pédeboscq Denis Gravier Françoise Casadebaig Geneviève Hou Arnaud Gissot Christophe Rey François Ichas Francesca De Giorgi Lydia Lartigue Jean-Paul Pometan 《Bioorganic & medicinal chemistry》2012,20(22):6724-6731
Monoclonal antibodies (MoAb) and tyrosine kinase inhibitors (TKI) targeting the EGFR (Epidermal Growth Factor Receptor) pathways are currently used in colorectal cancer treatment. Despite the improvement of median overall survival, resistance is observed notably due to KRAS and BRAF gene mutations. We synthesized four series of thienopyrimidines whose scaffold is structurally close to TKI used in clinical practice. We evaluated apoptosis induced by these compounds using flow cytometry on KRAS and BRAF mutated cell lines. Our results confirm that the mutated cell lines (HCT116 and HT29) are more resistant to apoptosis than the non-mutated cell line (Hela). Interestingly, among the 13 compounds tested, three of them (5b, 6b and 6d) and gefitinib exhibited a noteworthy pro-apoptotic effect, especially on mutated cell lines with an IC50 value between 70 and 110 μM. These three compounds seem particularly attractive for the development of novel treatments for colorectal cancer patients harboring EGFR pathway mutations. 相似文献
54.
Plant and Soil - Plant P acquisition strategies are driven by multiple belowground morphological and physiological traits as well as interactions among these traits. This study aimed to... 相似文献
55.
Tetramethylpyrazine scavenges superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes 总被引:14,自引:0,他引:14
Tetramethylpyrazine is one of the active ingredients of the Chinese herb Ligusticum wallichii Franchat. By electron spin resonance spin trapping methods, effects of tetramethylpyrazine on superoxide anion and nitric oxide generated by human polymorphonuclear leukocytes were studied. During the respiratory burst of polymorphonuclear leukocytes induced by N-formylmethionyl-leucyl-phenylalanine, tetramethylpyrazine scavenges superoxide anion dose-dependently, and decreases the production of nitric oxide significantly, but shows no influence on oxygen consumption. These results suggest that the effective protection of tetramethylpyrazine against ischemic brain injury might be due to its scavenging of reactive oxygen species and regulation on nitric oxide production, and consequent prevention of peroxynitrite formation. 相似文献
56.
Xin Li Tian-Tian Li Xiao-Hui Zhang Li-Fei Hou Xiao-Qian Yang Feng-Hua Zhu Wei Tang Jian-Ping Zuo 《PloS one》2013,8(8)
Background
Artemisinin analogue SM934 was previously reported to possess immunosuppressive properties. The aim of this study was to determine the effects and the underlying mechanisms of SM934 in murine experimental autoimmune encephalomyelitis (EAE).Methods
Female C57BL/6 mice immunized with MOG35–55 were treated with or without SM934, then the clinical scores and other relevant parameters were assessed. Th1, Th17 and regulatory T (Treg) cell profiles were determined through ELISA, qRT-PCR, flow cytometry and BrdU incorporation assay. The effects of SM934 on Th1, Th17 and Treg cells differentiation were explored through intracellular staining and flow cytometry examination.Results
In vivo, administration of SM934 significantly inhibited the development of EAE and suppressed the elevation of serum IL-17. Ex vivo, upon antigen-recall stimulation, IL-2, IFN-γ, IL-17 and IL-6 production were decreased, whereas IL-10 and TGF-β production were increased from the splenocytes isolated from SM934-treated mice. Consistently, both flow cytometry and qRT-PCR results showed that SM934 treatment significantly increased the Treg, while strongly suppressed the Th17 and Th1, responses in the peripheral. Furthermore, in the spinal lesion, SM934 treatment dramatically decreased the infiltration of CD4+ T cells, within which the Treg cells percentage was enlarged, whereas the Th17, but not Th1 percentage, was significantly decreased comparing with the vehicle-treated groups. Finally, both BrdU incorporation and in vitro Treg differentiation assays revealed that SM934 treatment could directly promote the expansion of Treg cells in vivo and in vitro.Conclusion
Taken together, this study demonstrated that SM934 treatment could ameliorate the murine EAE disease, which might be mediated by inducing Treg differentiation and expansion. 相似文献57.
Jun Zhang Kevin A. Fengler John L. Van Hemert Rajeev Gupta Nick Mongar Jindong Sun William B. Allen Yang Wang Benjamin Weers Hua Mo Renee Lafitte Zhenglin Hou Angela Bryant Farag Ibraheem Jennifer Arp Kankshita Swaminathan Stephen P. Moose Bailin Li Bo Shen 《Plant biotechnology journal》2019,17(12):2272-2285
58.
Qi Ye Ming Yan Lin Xu Hou Cao Zhenjiang Li Yong Chen Shuya Li Hanjie Ying 《Biotechnology letters》2009,31(4):537-542
An NADPH-dependent carbonyl reductase (PsCR) gene from Pichia stipitis was cloned. It contains an open reading frame of 849 bp encoding 283 amino acids whose sequence had less than 60% identity
to known reductases that produce ethyl (S)-4-chloro-3-hydroxybutanoates (S-CHBE). When expressed in Escherichia coli, the recombinant PsCR exhibited an activity of 27 U/mg using ethyl 4-chloro-3-oxobutanoate (COBE) as a substrate. Reduction
of COBE to (S)-CHBE by transformants in an aqueous mono-phase system for 18 h, gave a molar yield of 94% and an optical purity of the (S)-isomer of more than 99% enantiomeric excess. 相似文献
59.
In this paper we describe the cloning, expression and identification study of the TIP30 gene from amphioxus (Branchiostoma belcheri). The amphioxus TIP30 cDNA is comprised of 1499 bp and is translated in one open-reading frame to give a protein of 237 amino acids, with a predicted 23 amino acids signal peptide, a 147 bp 5'-UTR and a 638 bp 3'-UTR. A multiple alignment of TIP30 from amphioxus with other known TIP30 sequences shows the conservation of most amino acid residues involved in the peculiar structural domains found within TIP30's. Phylogenetic analysis places AmphiTIP30 at the base of the phylogenetic tree, suggesting that AmphiTIP30 is the archetype of the vertebrate TIP30 genes. We express the amphioxus TIP30 gene in Escherichia coli. driven by T7 promoter. The recombinant amphioxus TIP30 protein was purified by HisTrap affinity column. Subsequently, the binding constant and enzyme activity was mensurated. Western blot and immunohistochemistry analysis confirmed that amphioxus has a native molecular mass of approximately 26 kDa, and TIP30 was strongly expressed in ovary. Finally, the initial function of TIP30 is discussed. 相似文献
60.
Charles Jia-Yin Hou Cheng-Ho Tsai Cheng-Huang Su Yih-Jer Wu Su-Jen Chen Jing-Jing Chiu Ming-Shi Shiao Hung-I Yeh 《The journal of histochemistry and cytochemistry》2008,56(8):745-752
We examined the endothelial gap junctions in diabetic hyperlipidemic mice. Male apolipoprotein E (apoE)-deficient mice were made diabetic by streptozotocin. Three weeks later, the animals were treated with simvastatin for 2 weeks. The expression of aortic gap junctions in the non-diabetic (n=10), untreated diabetic (n=10), and simvastatin-treated diabetic animals (n=6) was analyzed. There was a >4-fold increase in serum cholesterol level and >50% increase in plaque areas in the diabetic mice, regardless of simvastatin treatment. Western blotting of aortae showed reduced expression of connexin37 (Cx37) and Cx40 in the diabetic mice, which were further decreased in the simvastatin-treated diabetic mice. Immunoconfocal microscopy showed that endothelial gap junctions made of Cx37 and Cx40 were both reduced in the untreated diabetic mice compared with the non-diabetic mice (decrease: Cx37, 41%; Cx40, 42%; both p<0.01). The reduction was greater in the simvastatin-treated mice (decrease in treated diabetic vs non-diabetic: Cx37, 61%; Cx40, 79%; both p<0.01; decrease in treated diabetic vs untreated diabetic: Cx37, 34%; Cx40, 63%; both p<0.01). Cx37 and Cx40 were decreased in the endothelium of plaque surface. Cx43 appeared in the medial layer and inner layer of the intima. All three connexins were rarely expressed in monocytes/macrophages inside the plaques. In conclusion, in apoE-deficient mice, streptozotocin-induced diabetes is associated with downregulation of endothelial Cx37 and Cx40 gap junctions. Short-term treatment with simvastatin exacerbates the downregulation. 相似文献