全文获取类型
收费全文 | 1479篇 |
免费 | 128篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 28篇 |
2020年 | 28篇 |
2019年 | 27篇 |
2018年 | 39篇 |
2017年 | 48篇 |
2016年 | 50篇 |
2015年 | 69篇 |
2014年 | 79篇 |
2013年 | 107篇 |
2012年 | 117篇 |
2011年 | 94篇 |
2010年 | 71篇 |
2009年 | 68篇 |
2008年 | 84篇 |
2007年 | 61篇 |
2006年 | 81篇 |
2005年 | 74篇 |
2004年 | 56篇 |
2003年 | 52篇 |
2002年 | 51篇 |
2001年 | 37篇 |
2000年 | 33篇 |
1999年 | 40篇 |
1998年 | 10篇 |
1997年 | 15篇 |
1996年 | 18篇 |
1995年 | 15篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 15篇 |
1990年 | 15篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 11篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 2篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1964年 | 1篇 |
排序方式: 共有1607条查询结果,搜索用时 31 毫秒
71.
V. M. Tuset J. L. Otero‐Ferrer J. Gómez‐Zurita L. A. Venerus C. Stransky R. Imondi A. M. Orlov Z. Ye L. Santschi P. K. Afanasiev L. Zhuang M. Farré M.S. Love A. Lombarte 《Journal of evolutionary biology》2016,29(10):2083-2097
The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures. 相似文献
72.
Anabel Fernndez‐Iglesias Martí Ortega‐Ribera Sergi Guix‐Muntet Jordi Gracia‐Sancho 《Journal of cellular and molecular medicine》2019,23(2):877-886
Liver cells isolated from pre‐clinical models are essential tools for studying liver (patho)physiology, and also for screening new therapeutic options. We aimed at developing a new antibody‐free isolation method able to obtain the four main hepatic cell types (hepatocytes, liver sinusoidal endothelial cells [LSEC], hepatic macrophages [HMΦ] and hepatic stellate cells [HSC]) from a single rat liver. Control and cirrhotic (CCl4 and TAA) rat livers (n = 6) were perfused, digested with collagenase and mechanically disaggregated obtaining a multicellular suspension. Hepatocytes were purified by low revolution centrifugations while non‐parenchymal cells were subjected to differential centrifugation. Two different fractions were obtained: HSC and mixed LSEC + HMΦ. Further LSEC and HMΦ enrichment was achieved by selective adherence time to collagen‐coated substrates. Isolated cells showed high viability (80%‐95%) and purity (>95%) and were characterized as functional: hepatocytes synthetized albumin and urea, LSEC maintained endocytic capacity and in vivo fenestrae distribution, HMΦ increased expression of inflammatory markers in response to LPS and HSC were activated upon in vitro culture. The 4 in 1 protocol allows the simultaneous isolation of highly pure and functional hepatic cell sub‐populations from control or cirrhotic single livers without antibody selection. 相似文献
73.
Roman Zoss Fernando Medina Ferrer Beverly E. Flood Daniel S. Jones Deon.C. Louw Jake Bailey 《Geobiology》2019,17(1):76-90
The processes that lead to the precipitation of authigenic calcium phosphate minerals in certain marine pore waters remain poorly understood. Phosphogenesis occurs in sediments beneath some oceanic upwelling zones that harbor polyphosphate‐accumulating bacteria. These bacteria are believed to concentrate phosphate in sediment pore waters, creating supersaturated conditions with respect to apatite precursors. However, the relationship between microbes and phosphorite formation is not fully resolved. To further study this association, we examined microbial community data generated from two sources: sediment cores recovered from the shelf of the Benguela upwelling region where phosphorites are currently forming, and DNA preserved within phosphoclasts recovered from a phosphorite deposit along the Benguela shelf. iTag and clone library sequencing of the 16S rRNA gene showed that many of our sediment‐hosted communities shared large numbers of phylotypes with one another, and that the same metabolic guilds were represented at localities across the shelf. Sulfate‐reducing bacteria and sulfur‐oxidizing bacteria were particularly abundant in our datasets, as were phylotypes that are known to carry out nitrification and the anaerobic oxidation of ammonium. The DNA extracted from phosphoclasts contained the signature of a distinct microbial community from those observed in the modern sediments. While some aspects of the modern and phosphoclast communities were similar, we observed both an enrichment of certain common microbial classes found in the modern phosphogenic sediments and a relative depletion of others. The phosphoclast‐associated DNA could represent a relict signature of one or more microbial assemblages that were present when the apatite or its precursors precipitated. While these taxa may or may not have contributed to the precipitation of the apatite that now hosts their genetic remains, several groups represented in the phosphoclast extract dataset have the genetic potential to metabolize polyphosphate, and perhaps modulate phosphate concentrations in pore waters where carbonate fluorapatite (or its precursors) are known to be precipitating. 相似文献
74.
Samarjit Patnaik Dipanwita Basu Noel Southall Seameen Dehdashti Kanny K. Wan Wei Zheng Marc Ferrer Mercedes Taylor Daniel A. Engel Juan Jose Marugan 《Bioorganic & medicinal chemistry letters》2019,29(9):1113-1119
Nonstructural protein 1 (NS1) plays a crucial function in the replication, spread, and pathogenesis of influenza virus by inhibiting the host innate immune response. Here we report the discovery and optimization of novel pyrazolopyridine NS1 antagonists that can potently inhibit influenza A/PR/8/34 replication in MDCK cells, rescue MDCK cells from cytopathic effects of seasonal influenza A strains, reverse NS1-dependent inhibition of IFN-β gene expression, and suppress the slow growth phenotype in NS1-expressing yeast. These pyrazolopyridines will enable researchers to investigate NS1 function during infection and how antagonists can be utilized in the next generation of treatments for influenza infection. 相似文献
75.
Joaquín Dalla Rizza Lía M. Randall Javier Santos Gerardo Ferrer‐Sueta Ana Denicola 《Protein science : a publication of the Protein Society》2019,28(1):191-201
Peroxiredoxins are thiol‐dependent peroxidases that function in peroxide detoxification and H2O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2O2 with rate constants of ca 2 × 103 M?1 s?1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s?1 for PRDX1, 0.2 s?1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study. 相似文献
76.
Yalitza Lopez Corcino Shekina Gonzalez Ferrer Luz Eliana Mantilla Sophia Trikeriotis Jin‐Sang Yu Steven Kim Samuel Hansen Jose‐Andres C. Portillo Carlos S. Subauste 《Cellular microbiology》2019,21(10)
Toxoplasma gondii causes retinitis and encephalitis. Avoiding targeting by autophagosomes is key for its survival because T. gondii cannot withstand lysosomal degradation. During invasion of host cells, T. gondii triggers epidermal growth factor receptor (EGFR) signalling enabling the parasite to avoid initial autophagic targeting. However, autophagy is a constitutive process indicating that the parasite may also use a strategy operative beyond invasion to maintain blockade of autophagic targeting. Finding that such a strategy exists would be important because it could lead to inhibition of host cell signalling as a novel approach to kill the parasite in previously infected cells and treat toxoplasmosis. We report that T. gondii induced prolonged EGFR autophosphorylation. This effect was mediated by PKCα/PKCβ ? Src because T. gondii caused prolonged activation of these molecules and their knockdown or incubation with inhibitors of PKCα/PKCβ or Src after host cell invasion impaired sustained EGFR autophosphorylation. Addition of EGFR tyrosine kinase inhibitor (TKI) to previously infected cells led to parasite entrapment by LC3 and LAMP‐1 and pathogen killing dependent on the autophagy proteins ULK1 and Beclin 1 as well as lysosomal enzymes. Administration of gefitinib (EGFR TKI) to mice with ocular and cerebral toxoplasmosis resulted in disease control that was dependent on Beclin 1. Thus, T. gondii promotes its survival through sustained EGFR signalling driven by PKCα/β ? Src, and inhibition of EGFR controls pre‐established toxoplasmosis. 相似文献
77.
Nuria Pujol-Carrion Alma Gonzalez-Alfonso Sergi Puig Maria Angeles de la Torre-Ruiz 《Microbial biotechnology》2022,15(5):1525-1541
Ferritin proteins have an enormous capacity to store iron in cells. In search for the best conditions to accumulate and store bioavailable iron, we made use of a double mutant null for the monothiol glutaredoxins GRX3 and GRX4. The strain grx3grx4 accumulates high iron concentrations in the cytoplasm, making the metal easily available for ferritin chelation. Here, we perform a comparative study between human (L and H) and soya bean ferritins (H1 and H2) function in the eukaryotic system Saccharomyces cerevisiae. We demonstrate that the four human and soya bean ferritin chains are successfully expressed in our model system. Upon coexpression of either both human or soya bean ferritin chains, respiratory conditions along with iron supplementation led us to obtain the maximum yields of iron stored in yeast described to date. Human and soya bean ferritin chains are functional and present equivalent properties as promoters of cell survival in iron overload conditions. The best system revealed that the four human and soya bean ferritins possess a novel function as anti-ageing proteins in conditions of iron excess. In this respect, both ferritin chains with oxidoreductase capacity (human-H and soya bean-H2) bear the highest capacity to extend life suggesting the possibility of an evolutionary conservation. 相似文献
78.
79.
Chaves DF Ferrer PP de Souza EM Gruz LM Monteiro RA de Oliveira Pedrosa F 《Proteomics》2007,7(20):3759-3763
Herbaspirillum seropedicae is an endophytic diazotroph associated with economically important crops such as rice, sugarcane, and wheat. Here, we present a 2-D reference map for H. seropedicae. Using MALDI-TOF-MS we identified 205 spots representing 173 different proteins with a calculated average of 1.18 proteins/gene. Seventeen hypothetical or conserved hypothetical ORFs were shown to code for true gene products. These data will support the genome annotation process and provide a basis on which to undertake comparative proteomic studies. 相似文献
80.
The names Quercus ballota and Q. rotundifolia (Fagaceae), referring to taxa sometimes considered conspecific with the widely distributed Q. ilex, are discussed and typified. A specimen preserved at MPU is designated as the lectotype of Desfontaines's name Q. ballota. Lamarck's name Q. rotundifolia is neotypified using a specimen preserved at VAL, with several duplicates in other European herbaria. 相似文献