全文获取类型
收费全文 | 1965篇 |
免费 | 139篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 21篇 |
2019年 | 19篇 |
2018年 | 23篇 |
2017年 | 27篇 |
2016年 | 29篇 |
2015年 | 55篇 |
2014年 | 83篇 |
2013年 | 116篇 |
2012年 | 100篇 |
2011年 | 127篇 |
2010年 | 73篇 |
2009年 | 66篇 |
2008年 | 126篇 |
2007年 | 128篇 |
2006年 | 111篇 |
2005年 | 117篇 |
2004年 | 114篇 |
2003年 | 85篇 |
2002年 | 87篇 |
2001年 | 45篇 |
2000年 | 60篇 |
1999年 | 44篇 |
1998年 | 36篇 |
1997年 | 25篇 |
1996年 | 27篇 |
1995年 | 34篇 |
1994年 | 18篇 |
1993年 | 6篇 |
1992年 | 25篇 |
1991年 | 24篇 |
1990年 | 25篇 |
1989年 | 17篇 |
1988年 | 20篇 |
1987年 | 19篇 |
1986年 | 10篇 |
1985年 | 16篇 |
1984年 | 19篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 16篇 |
1976年 | 6篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 7篇 |
排序方式: 共有2104条查询结果,搜索用时 31 毫秒
991.
In mycoplasmal pneumonia, the bronchi are histopathologically filled with polymorphonuclear leukocytes. The EGFR pathway is involved in IL-8 production. We investigated the contribution of the EGFR pathway to IL-8 production by bronchial epithelial cells (A549) stimulated with Mp-Ag. The IL-8 production by A549 cells stimulated with Mp-Ag was decreased by the addition of an EGFR kinase inhibitor or transfection with small interfering RNA against EGFR. The levels of epiregulin mRNA in A549 cells were increased by stimulation with Mp-Ag. In conclusion, the EFGR pathway participates in IL-8 production by bronchial epithelial cells stimulated with Mp-Ag. 相似文献
992.
Ichihara H Hino M Makizono T Umebayashi M Matsumoto Y Ueoka R 《Bioorganic & medicinal chemistry letters》2011,21(1):207-210
Inhibitory effects of HL-n composed of 95 mol % l-α-dimyristoylphosphatidylcholin (DMPC) and 5 mol % polyoxyethylenedodecylether (C12(EO)n, n = 21, 23, or 25) on the growth of human rheumatoid arthritis (RA) fibroblast-like synoviocytes (HFLS-RA) in vitro were examined. Remarkably high inhibitory effects of HL-n on the growth of HFLS-RA cells were obtained. The induction of apoptosis by HL-n was revealed on the basis of TUNEL method. Furthermore, the therapeutic effects of HL-23 using mouse models of arthritis were investigated. Therapeutic effects without joint swelling were obtained in mouse models of RA treated with HL. 相似文献
993.
Stotz HU Sawada Y Shimada Y Hirai MY Sasaki E Krischke M Brown PD Saito K Kamiya Y 《The Plant journal : for cell and molecular biology》2011,67(1):81-93
Plant secondary metabolites are known to facilitate interactions with a variety of beneficial and detrimental organisms, yet the contribution of specific metabolites to interactions with fungal pathogens is poorly understood. Here we show that, with respect to aliphatic glucosinolate‐derived isothiocyanates, toxicity against the pathogenic ascomycete Sclerotinia sclerotiorum depends on side chain structure. Genes associated with the formation of the secondary metabolites camalexin and glucosinolate were induced in Arabidopsis thaliana leaves challenged with the necrotrophic pathogen S. sclerotiorum. Unlike S. sclerotiorum, the closely related ascomycete Botrytis cinerea was not identified to induce genes associated with aliphatic glucosinolate biosynthesis in pathogen‐challenged leaves. Mutant plant lines deficient in camalexin, indole, or aliphatic glucosinolate biosynthesis were hypersusceptible to S. sclerotiorum, among them the myb28 mutant, which has a regulatory defect resulting in decreased production of long‐chained aliphatic glucosinolates. The antimicrobial activity of aliphatic glucosinolate‐derived isothiocyanates was dependent on side chain elongation and modification, with 8‐methylsulfinyloctyl isothiocyanate being most toxic to S. sclerotiorum. This information is important for microbial associations with cruciferous host plants and for metabolic engineering of pathogen defenses in cruciferous plants that produce short‐chained aliphatic glucosinolates. 相似文献
994.
Chibazakura T Kamachi K Ohara M Tane S Yoshikawa H Roberts JM 《Molecular and cellular biology》2011,31(2):248-255
Cyclin A is known to promote S-phase entry in mammals, but its critical targets in this process have not been defined. We derived a novel human cyclin A mutant (CycA-C1), which can activate cyclin-dependent kinase but cannot promote S-phase entry, and isolated replication licensing factor Mcm7 as a factor that interacts with the wild-type cyclin A but not with the mutant. We demonstrated that human cyclin A and Mcm7 interact in the chromatin fraction. To address the physiological significance of the cyclin A-Mcm7 interaction, we isolated an Mcm7 mutant (Mcm7-3) that is capable of association with CycA-C1 and found that it can also suppress the deficiency of CycA-C1 in promoting S-phase entry. Finally, RNA interference experiments showed that the CycA-C1 mutant is defective for the endogenous cyclin A function in S-phase entry and that this defect can be suppressed by the Mcm7-3 mutant. Our findings demonstrate that interaction with Mcm7 is essential for the function of cyclin A in promoting S-phase entry. 相似文献
995.
Ueda T Shikano M Kamiya T Joh T Ugawa S 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(1):G138-G147
The esophageal epithelium has sensory properties that enable it to sustain normal barrier function. Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable channel that is activated by extracellular hypotonicity, polyunsaturated fatty acids, phorbol esters, and elevated temperature. We found that TRPV4 is expressed in both human esophageal tissue and in HET-1A cells, a human esophageal epithelial cell line. Specific activation of TRPV4 by the phorbol ester 4α-phorbol 12,13-didecanoate (4α-PDD) increased intracellular Ca(2+) in a subset of HET-1A cells. Elevated temperature strongly potentiated this effect at low concentrations of 4α-PDD, and all of the responses were inhibited by the TRPV antagonist ruthenium red. TRPV4 activation differentially affected cell proliferation and cell viability; HET-1A cell proliferation was increased by 1 μM 4α-PDD, whereas higher concentrations (10 μM and 30 μM) significantly decreased cell viability. Transient TRPV4 activation triggered ATP release in a concentration-dependent manner via gap-junction hemichannels, including pannexin 1 and connexin 43. Furthermore, TRPV4 activation for 24 h did not increase the production of interleukin 8 (IL-8) but reduced IL-1β-induced IL-8 production. Small-interference RNA targeted to TRPV4 significantly attenuated all of the 4α-PDD-induced responses in HET-1A cells. Collectively, these findings suggest that TRPV4 is a novel regulator of Ca(2+)-dependent signaling pathways linked to cell proliferation, cell survival, ATP release, and IL-8 production in human esophageal epithelial cells. 相似文献
996.
Establishment of intestinal epithelial cell lines from adult mouse small and large intestinal crypts 总被引:1,自引:0,他引:1
Iwamoto T Yamada K Shimizu M Totsuka M 《Bioscience, biotechnology, and biochemistry》2011,75(5):925-929
Small and large intestinal epithelial cell (IEC) lines were established from adult murine intestinal crypts. Both established small and large IECs line (named aMoS7 and aMoC1 respectively) expressed epithelial markers. Similarly to IECs isolated from adult mouse intestines, the expression of major histocompatibility complex (MHC) class II molecules was induced by interferon-γ-treatment in both established cell lines. This expression of MHC class II molecules was higher in small intestinal aMoS7 cells than in large intestinal aMoC1 cells. Treatment with lipopolysaccharide and with ligands of Toll-like receptors 1, 2, 3, and 7 induced secretion of interleukin-6 from both adult IEC lines. These results suggest that the aMoS7 and aMoC1 cell lines can serve as useful tools in analyzing the immunological functions of IECs, especially in studying the IEC response to microbial components and its antigen presenting ability. 相似文献
997.
998.
Mina Okochi Taku Matsumura and Shuhei Yamamoto Eiichi Nakayama Kowichi Jimbow Hiroyuki Honda 《Biotechnology progress》2013,29(1):135-142
A three‐dimensional (3D) multicellular tumor spheroid culture array has been fabricated using a magnetic force‐based cell patterning method, analyzing the effect of stromal fibroblast on the invasive capacity of melanoma. Formation of spheroids was observed when array‐like multicellular patterns of melanoma were developed using a pin‐holder device made of magnetic soft iron and an external magnet, which enables the assembly of the magnetically labeled cells on the collagen gel‐coated surface as array‐like cell patterns. The interaction of fibroblast on the invasion of melanoma was investigated using three types of cell interaction models: (i) fibroblasts were magnetically labeled and patterned together in array with melanoma spheroids (direct‐interaction model), (ii) fibroblasts coexisting in the upper collagen gel (indirect‐interaction model) of melanoma spheroids, and (iii) fibroblast‐sheets coexisting under melanoma spheroids (fibroblast‐sheet model). The fibroblast‐sheet model has largely increased the invasive capacity of melanoma, and the promotion of adhesion, migration, and invasion were also observed. In the fibroblast‐sheet model, the expression of IL‐8 and MMP‐2 increased by 24‐fold and 2‐fold, respectively, in real time RT‐PCR compared to the absence of fibroblasts. The results presented in this study demonstrate the importance of fibroblast interaction to invasive capacity of melanoma in the 3D in vitro bioengineered tumor microenvironment. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013 相似文献
999.
1000.
Sayoko Negi Mitsuaki Sawano Shun Kohsaka Taku Inohara Yasuyuki Shiraishi Takashi Kohno Yuichiro Maekawa Motoaki Sano Tsutomu Yoshikawa Keiichi Fukuda 《PloS one》2014,9(5)