全文获取类型
收费全文 | 6186篇 |
免费 | 456篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 24篇 |
2022年 | 59篇 |
2021年 | 114篇 |
2020年 | 72篇 |
2019年 | 84篇 |
2018年 | 150篇 |
2017年 | 112篇 |
2016年 | 193篇 |
2015年 | 334篇 |
2014年 | 388篇 |
2013年 | 457篇 |
2012年 | 559篇 |
2011年 | 518篇 |
2010年 | 319篇 |
2009年 | 282篇 |
2008年 | 392篇 |
2007年 | 365篇 |
2006年 | 352篇 |
2005年 | 292篇 |
2004年 | 319篇 |
2003年 | 220篇 |
2002年 | 217篇 |
2001年 | 139篇 |
2000年 | 99篇 |
1999年 | 89篇 |
1998年 | 58篇 |
1997年 | 41篇 |
1996年 | 30篇 |
1995年 | 30篇 |
1994年 | 32篇 |
1993年 | 29篇 |
1992年 | 35篇 |
1991年 | 33篇 |
1990年 | 31篇 |
1989年 | 36篇 |
1988年 | 9篇 |
1987年 | 21篇 |
1986年 | 11篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1976年 | 3篇 |
1973年 | 3篇 |
1964年 | 3篇 |
排序方式: 共有6643条查询结果,搜索用时 906 毫秒
191.
Cho Bumrae Lee Eun-Jin Ahn Sun Mi Kim Ghangyong Lee Sang Hoon Ji Dal-Young Kang Jung-Taek 《Transgenic research》2019,28(5-6):549-559
Transgenic Research - Islet xenotransplantation is a promising treatment for type I diabetes. Numerous studies of islet xenotransplantation have used pig-to-nonhuman primate transplantation models.... 相似文献
192.
Woong-Hee Kim Pyeonghwa Jeong Seon-Wook Kim Haaglim Cho Jeong-min Lee Shinae Seo Haihong Shen Youngkeun Ahn Da-Woon Jung Yong-Chul Kim Darren R. Williams 《Bioorganic & medicinal chemistry》2019,27(13):2923-2934
Indirubin-based compounds affect diverse biological processes, such as inflammation and angiogenesis. In this study, we tested a novel indirubin derivative, LDD-1819 (2-((((2Z,3E)-5-hydroxy-5′-nitro-2′-oxo-[2,3′-biindolinylidene]-3-ylidene)amino)oxy)ethan-1-aminium chloride) for two major biological activities: cell plasticity and anti-cancer activity. Biological assays indicated that LDD-1819 induced somatic cell plasticity. LDD-1819 potentiated myoblast reprogramming into osteogenic cells and fibroblast reprogramming into adipogenic cells. Interestingly, in an assay of skeletal muscle dedifferentiation, LDD-1819 induced human muscle cellularization and blocked residual proliferative activity to produce a population of mononuclear refractory cells, which is also observed in the early stages of limb regeneration in urodele amphibians. In cancer cell lines, LDD-1819 treatment inhibited cell invasion and selectively induced apoptosis compared to normal cells. In an animal tumor xenograft model, LDD-1819 reduced human cancer cell metastasis in vivo at doses that did not produce toxicity. Biochemical assays showed that LDD-1819 possessed inhibitory activity against glycogen synthase kinase-3β, which is linked to cell plasticity, and aurora kinase, which regulates carcinogenesis. These results indicate that novel indirubin derivative LDD-1819 is a dual inhibitor of glycogen synthase kinase-3β and aurora A kinase, and has potential for development as an anti-cancer drug or as a reprogramming agent for cell-therapy based approaches to treat degenerative diseases. 相似文献
193.
Dawn Chiniquy William Underwood Jason Corwin Andrew Ryan Heidi Szemenyei Candice C. Lim Solomon H. Stonebloom Devon S. Birdseye John Vogel Daniel Kliebenstein Henrik V. Scheller Shauna Somerville 《The Plant journal : for cell and molecular biology》2019,100(5):1022-1035
Powdery mildew (Golovinomyces cichoracearum), one of the most prolific obligate biotrophic fungal pathogens worldwide, infects its host by penetrating the plant cell wall without activating the plant's innate immune system. The Arabidopsis mutant powdery mildew resistant 5 (pmr5) carries a mutation in a putative pectin acetyltransferase gene that confers enhanced resistance to powdery mildew. Here, we show that heterologously expressed PMR5 protein transfers acetyl groups from [14C]‐acetyl‐CoA to oligogalacturonides. Through site‐directed mutagenesis, we show that three amino acids within a highly conserved esterase domain in putative PMR5 orthologs are necessary for PMR5 function. A suppressor screen of mutagenized pmr5 seed selecting for increased powdery mildew susceptibility identified two previously characterized genes affecting the acetylation of plant cell wall polysaccharides, RWA2 and TBR. The rwa2 and tbr mutants also suppress powdery mildew disease resistance in pmr6, a mutant defective in a putative pectate lyase gene. Cell wall analysis of pmr5 and pmr6, and their rwa2 and tbr suppressor mutants, demonstrates minor shifts in cellulose and pectin composition. In direct contrast to their increased powdery mildew resistance, both pmr5 and pmr6 plants are highly susceptibile to multiple strains of the generalist necrotroph Botrytis cinerea, and have decreased camalexin production upon infection with B. cinerea. These results illustrate that cell wall composition is intimately connected to fungal disease resistance and outline a potential route for engineering powdery mildew resistance into susceptible crop species. 相似文献
194.
195.
196.
The possibility of improving a two-stage (68 degrees C/55 degrees C) anaerobic digestion concept for treatment of cattle manure was studied. In batch experiments, a 10-24% increase of the specific methane yield from cattle manure and its fractions was obtained, when the substrates were inoculated with bacteria of the genus Caldicellusiruptor and Dictyoglomus. In a reactor experiment inoculation of a 68 degrees C pretreatment reactor with Caldicellusiruptor resulted in a 93% increase in the methane yield of the pretreatment reactor for a period of 18 days, but gave only a slight increase in the overall methane yield of the two-stage setup. 相似文献
197.
Glycosphingolipids with extended sugar chain have specialized functions in development and behavior of Drosophila 总被引:2,自引:0,他引:2
Chen YW Pedersen JW Wandall HH Levery SB Pizette S Clausen H Cohen SM 《Developmental biology》2007,306(2):736-749
Glycosphingolipids (GSL) are glycosylated polar lipids in cell membranes essential for development of vertebrates as well as Drosophila. Mutants that impair enzymes involved in biosynthesis of GSL sugar chains provide a means to assess the functions of the sugar chains in vivo. The Drosophila glycosyltransferases Egghead and Brainiac are responsible for the 2nd and 3rd steps of GSL sugar chain elongation. Mutants lacking these enzymes are lethal and the nature of the defects that occur has suggested that GSL might impact on signaling by the Notch and EGFR pathways. Here we report on characterization of enzymes involved in the 4th and 5th steps of GSL sugar chain elongation in vitro and explore the biological consequences of removing the enzymes involved in step 4 in vivo. Two beta4-N-Acetylgalactosyltransferase enzymes can carry out step 4 (beta4GalNAcTA and beta4GalNAcTB), and while they may have overlapping activity, the mutants produce distinct phenotypes. The beta4GalNAcTA mutant displays behavioral defects, which are also observed in viable brainiac mutants, suggesting that proper locomotion and coordination primarily depend on GSL elongation. beta4GalNAcTB mutant animal shows ventralization of ovarian follicle cells, which is caused by defective EGFR signaling between the oocyte and the dorsal follicle cells to specify dorsal fate. GSL sequentially elongated by Egh, Brn and beta4GalNAcTB in the oocyte contribute to this signaling pathway. Despite the similar enzymatic activity, we provide evidence that the two enzymes are not functionally redundant in vivo, but direct distinct developmental functions of GSL. 相似文献
198.
A recombinant DING protein from Pseudomonas fluorescens has been previously shown to have a phosphate-binding site, and to be mitogenic for human cells. Here we report the three-dimensional structure of the protein, confirming a close similarity to the "Venus flytrap" structure seen in other human and bacterial phosphate-binding proteins. Site-directed mutagenesis confirms the role of a key residue involved in phosphate binding, and that the mitogenic activity is not dependent on this property. Deletion of one of the two hinged domains that constitute the Venus flytrap also eliminates phosphate binding whilst enhancing mitogenic activity. 相似文献
199.
Hersleth HP Uchida T Røhr AK Teschner T Schünemann V Kitagawa T Trautwein AX Görbitz CH Andersson KK 《The Journal of biological chemistry》2007,282(32):23372-23386
High resolution crystal structures of myoglobin in the pH range 5.2-8.7 have been used as models for the peroxide-derived compound II intermediates in heme peroxidases and oxygenases. The observed Fe-O bond length (1.86-1.90 A) is consistent with that of a single bond. The compound II state of myoglobin in crystals was controlled by single-crystal microspectrophotometry before and after synchrotron data collection. We observe some radiation-induced changes in both compound II (resulting in intermediate H) and in the resting ferric state of myoglobin. These radiation-induced states are quite unstable, and compound II and ferric myoglobin are immediately regenerated through a short heating above the glass transition temperature (<1 s) of the crystals. It is unclear how this influences our compound II structures compared with the unaffected compound II, but some crystallographic data suggest that the influence on the Fe-O bond distance is minimal. Based on our crystallographic and spectroscopic data we suggest that for myoglobin the compound II intermediate consists of an Fe(IV)-O species with a single bond. The presence of Fe(IV) is indicated by a small isomer shift of delta = 0.07 mm/s from M?ssbauer spectroscopy. Earlier quantum refinements (crystallographic refinement where the molecular-mechanics potential is replaced by a quantum chemical calculation) and density functional theory calculations suggest that this intermediate H species is protonated. 相似文献
200.
Lars B Dahlin Kristina Erichs Charlotte Andersson Catharina Thornqvist Clas Backman Henrik Düppe Pelle Lindqvist Marianne Forslund 《Journal of brachial plexus and peripheral nerve injury》2007,2(1):1-5