全文获取类型
收费全文 | 2641篇 |
免费 | 185篇 |
专业分类
2826篇 |
出版年
2023年 | 18篇 |
2022年 | 31篇 |
2021年 | 68篇 |
2020年 | 32篇 |
2019年 | 42篇 |
2018年 | 46篇 |
2017年 | 47篇 |
2016年 | 93篇 |
2015年 | 168篇 |
2014年 | 168篇 |
2013年 | 185篇 |
2012年 | 259篇 |
2011年 | 204篇 |
2010年 | 130篇 |
2009年 | 113篇 |
2008年 | 151篇 |
2007年 | 153篇 |
2006年 | 124篇 |
2005年 | 141篇 |
2004年 | 127篇 |
2003年 | 112篇 |
2002年 | 75篇 |
2001年 | 14篇 |
2000年 | 17篇 |
1999年 | 28篇 |
1998年 | 20篇 |
1997年 | 15篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 15篇 |
1992年 | 14篇 |
1991年 | 11篇 |
1990年 | 16篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 11篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1974年 | 3篇 |
1972年 | 5篇 |
1966年 | 5篇 |
1931年 | 3篇 |
排序方式: 共有2826条查询结果,搜索用时 0 毫秒
991.
992.
Nadiya Byts Subodh Sharma Tarja Malm Mika Kaakinen Paula Korhonen Laura Jaakkonen Meike Keuters Mikko Huuskonen Ilkka Pietil Jari Koistinaho Peppi Koivunen Johanna Myllyharju 《The Journal of biological chemistry》2022,298(3)
Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of >300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effects. A transmembrane prolyl 4-hydroxylase (P4H-TM) is highly expressed in the brain and contributes to the regulation of HIF, but the outcome of its inhibition on stroke is yet unknown. To study this, we subjected WT and P4htm−/− mice to permanent middle cerebral artery occlusion (pMCAO). Lack of P4H-TM had no effect on lesion size following pMCAO, but increased inflammatory microgliosis and neutrophil infiltration was observed in the P4htm−/− cortex. Furthermore, both the permeability of blood brain barrier and ultrastructure of cerebral tight junctions were compromised in P4htm−/− mice. At the molecular level, P4H-TM deficiency led to increased expression of proinflammatory genes and robust activation of protein kinases in the cortex, while expression of tight junction proteins and the neuroprotective growth factors erythropoietin and vascular endothelial growth factor was reduced. Our data provide the first evidence that P4H-TM inactivation has no protective effect on infarct size and increases inflammatory microgliosis and neutrophil infiltration in the cortex at early stage after pMCAO. When considering HIF-P4H inhibitors as potential therapeutics in stroke, the current data support that isoenzyme-selective inhibitors that do not target P4H-TM or HIF-P4H-3 would be preferred. 相似文献
993.
The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis 总被引:5,自引:0,他引:5
J Li T McQuade AB Siemer J Napetschnig K Moriwaki YS Hsiao E Damko D Moquin T Walz A McDermott FK Chan H Wu 《Cell》2012,150(2):339-350
RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. Here, we report that?the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures. The fibrils exhibit classical characteristics of β-amyloids, as shown by Thioflavin T (ThT) and Congo red (CR) binding, circular dichroism, infrared spectroscopy, X-ray diffraction, and solid-state NMR. Structured amyloid cores are mapped in RIP1 and RIP3 that are flanked?by regions of mobility. The endogenous RIP1/RIP3 complex isolated from necrotic cells binds ThT, is ultrastable, and has a fibrillar core structure, whereas necrosis is partially inhibited by ThT, CR, and another amyloid dye, HBX. Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in?vivo. The current study provides insight into the structural changes that occur when RIP kinases are triggered to execute different signaling outcomes and expands the realm of amyloids to complex formation and signaling. 相似文献
994.
995.
Donohue K Dorn L Griffith C Kim E Aguilera A Polisetty CR Schmitt J 《Evolution; international journal of organic evolution》2005,59(4):758-770
Germination timing of Arabidopsis thaliana displays strong plasticity to geographic location and seasonal conditions experienced by seeds. We identified which plastic responses were adaptive using recombinant inbred lines in a field manipulation of geographic location (Kentucky, KY; Rhode Island, RI), maternal photoperiod (14-h and 10-h days), and season of dispersal (June and November). Transgressive segregation created novel genotypes that had either higher fitness or lower fitness in certain environments than either parent. Natural selection on germination timing and its variation explained 72% of the variance in fitness among genotypes in KY, 30% in June-dispersed seeds in RI, but only 4% in November-dispersed seeds in RI. Therefore, natural selection on germination timing is an extremely efficient sieve that can determine which genotypes can persist in some locations, and its efficiency is geographically variable and depends on other aspects of life history. We found no evidence for adaptive responses to maternal photoperiod during seed maturation. We did find adaptive plasticity to season of seed dispersal in RI. Seeds dispersed in June postponed germination, which was adaptive, while seeds dispersed in November accelerated germination, which was also adaptive. We also found maladaptive plasticity to geographic location for seeds dispersed in June, such that seeds dispersed in KY germinated much sooner than the optimum time. Consequently, bet hedging in germination timing was favorable in KY; genotypes with more variation in germination timing had higher fitness because greater variation was associated with postponed germination. Selection on germination timing varied across geographic location, indicating that germination timing can be a critical stage in the establishment of genotypes in new locations. The rate of evolution of germination timing may therefore strongly influence the rate at which species can expand their range. 相似文献
996.
997.
WDR11‐mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome 下载免费PDF全文
Yeon‐Joo Kim Daniel PS Osborn Ji‐Young Lee Masatake Araki Kimi Araki Timothy Mohun Johanna Känsäkoski Nina Brandstack Hyun‐Taek Kim Francesc Miralles Cheol‐Hee Kim Nigel A Brown Hyung‐Goo Kim Juan Pedro Martinez‐Barbera Paris Ataliotis Taneli Raivio Lawrence C Layman Soo‐Hyun Kim 《EMBO reports》2018,19(2):269-289
998.
Laccase-catalyzed polymerization of tyrosine-containing peptides 总被引:1,自引:0,他引:1
Mattinen ML Kruus K Buchert J Nielsen JH Andersen HJ Steffensen CL 《The FEBS journal》2005,272(14):3640-3650
Laccase-catalyzed polymerization of tyrosine and tyrosine-containing peptides was studied in the presence and absence of ferulic acid (FA). Advanced spectroscopic methods such as MALDI-TOF MS, EPR, FTIR microscopy and HPLC-fluorescence, as well as more conventional analytical tools: oxygen consumption measurements and SDS/PAGE were used in the reaction mechanism studies. Laccase was found to oxidize tyrosine and tyrosine-containing peptides, with consequent polymerization of the compounds. The covalent linkage connecting the compounds was found to be an ether bond. Only small amounts of dityrosine bonds were detected in the polymers. When FA was added to the reaction mixtures, it was found to be incorporated into the polymer structure. Thus, in addition to homopolymers, different heteropolymers containing two or four FA residues were formed in the reactions. 相似文献
999.
1000.