全文获取类型
收费全文 | 3081篇 |
免费 | 239篇 |
专业分类
3320篇 |
出版年
2024年 | 5篇 |
2023年 | 23篇 |
2022年 | 65篇 |
2021年 | 109篇 |
2020年 | 47篇 |
2019年 | 83篇 |
2018年 | 113篇 |
2017年 | 107篇 |
2016年 | 132篇 |
2015年 | 190篇 |
2014年 | 199篇 |
2013年 | 227篇 |
2012年 | 269篇 |
2011年 | 270篇 |
2010年 | 163篇 |
2009年 | 117篇 |
2008年 | 190篇 |
2007年 | 189篇 |
2006年 | 165篇 |
2005年 | 134篇 |
2004年 | 123篇 |
2003年 | 97篇 |
2002年 | 87篇 |
2001年 | 22篇 |
2000年 | 16篇 |
1999年 | 19篇 |
1998年 | 27篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 8篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1970年 | 1篇 |
1961年 | 3篇 |
1960年 | 1篇 |
排序方式: 共有3320条查询结果,搜索用时 15 毫秒
991.
Serpulids and other related tube-dwelling polychaetes are often ignored when found as fossil remains. They are, however, a widespread and important group today, and abundant literature has been published on them. Knowledge of fossil serpulids is centered on European material, and little has already been done on South American fossil calcareous tubes. In this paper, seven serpulid and sabellid morphotypes are described from the Early Cretaceous marine Agrio Formation of Argentina, revealing a diversity of worms recorded as encrusters on bivalves, ammonites and corals. Sabellids are represented by Glomerula cf. serpentina. Serpulids are represented by two subfamilies: “Serpulinae” includes Mucroserpula mucroserpula, Parsimonia antiquata, Placostegus cf. conchophilus, Propomatoceros semicostatus and P. sulcicarinatus; Spirorbinae is represented by heavily worn tiny coiled tubes assigned to ?Neomicrorbis. Serpulids and sabellids are one of the main components of the mollusk-encrusting fauna recorded in the Agrio Formation, along with small oysters but much more diverse. They are most commonly found as post-mortem encrusters, but some cases of unquestionable living interaction are also found, such as serpulid tubes embedded on coral branches. They are often overgrown by bryozoans, and sometimes by oysters; they frequently occur aggregated. 相似文献
992.
Dario A. Vitturi Chen-Shan Chen Steven R. Woodcock Sonia R. Salvatore Gustavo Bonacci Jeffrey R. Koenitzer Nicolas A. Stewart Nobunao Wakabayashi Thomas W. Kensler Bruce A. Freeman Francisco J. Schopfer 《The Journal of biological chemistry》2013,288(35):25626-25637
Inflammation, characterized by the activation of both resident and infiltrated immune cells, is accompanied by increased production of oxidizing and nitrating species. Nitrogen dioxide, the proximal nitrating species formed under these conditions, reacts with unsaturated fatty acids to yield nitroalkene derivatives. These electrophilic products modulate protein function via post-translational modification of susceptible nucleophilic amino acids. Nitroalkenes react with Keap1 to instigate Nrf2 signaling, activate heat shock response gene expression, and inhibit NF-κB-mediated signaling, inducing net anti-inflammatory and tissue-protective metabolic responses. We report the purification and characterization of a NADPH-dependent liver enzyme that reduces the nitroalkene moiety of nitro-oleic acid, yielding the inactive product nitro-stearic acid. Prostaglandin reductase-1 (PtGR-1) was identified as a nitroalkene reductase by protein purification and proteomic studies. Kinetic measurements, inhibition studies, immunological and molecular biology approaches as well as clinical analyses confirmed this identification. Overexpression of PtGR-1 in HEK293T cells promoted nitroalkene metabolism to inactive nitroalkanes, an effect that abrogated the Nrf2-dependent induction of heme oxygenase-1 expression by nitro-oleic acid. These results situate PtGR-1 as a critical modulator of both the steady state levels and signaling activities of fatty acid nitroalkenes in vivo. 相似文献
993.
Kyle Jansson Brenda S. Magenheimer Robin L. Maser James P. Calvet Gustavo Blanco 《The Journal of membrane biology》2013,246(7):581-590
Cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD) are abnormally sensitive to ouabain, responding to physiological ouabain concentrations with enhanced proliferation and increased forskolin-induced transepithelial fluid secretion. This requires activation of the epidermal growth factor receptor (EGFR), Src kinase and the extracellular signal-regulated kinases MEK and ERK. Here, we have determined if the ADPKD phenotype obtained in mouse cortical collecting duct cells by stable overexpression of the C-terminal domain of polycystin-1 (PC-1 C-tail) also elicits the ADPKD-like response to ouabain in the cells. M-1 C20 cells expressing the PC-1 C-tail and M-1 C17 cells lacking expression of this construct were treated with physiological concentrations of ouabain, and cell proliferation, activation of the EGFR-Src-MEK-ERK pathway, forskolin-induced transepithelial Cl? secretion and the sensitivity of Na,K-ATPase to ouabain were explored. M-1 C20 cells responded to ouabain with increased cell proliferation and ERK phosphorylation. Ouabain also augmented forskolin-induced and cystic fibrosis transmembrane conductance regulator-mediated apical secretion of Cl? in M-1 C20 cells. These effects required activation of EGFR, Src and MEK. In contrast, ouabain had no significant effects on M-1 C17 cells. Interestingly, approximately 20 % of the Na,K-ATPase from M-1 C20 cells presented an abnormally increased sensitivity to ouabain. Overexpression of PC-1 C-tail in M-1 C20 cells is associated with an ouabain-sensitive phenotype and an increased ability of the cells to proliferate and secrete anions upon ouabain stimulation. This phenotype mimics the ouabain sensitivity of ADPKD cells and may help promote their cystogenic potential. 相似文献
994.
Urtzi Enriquez-Urzelai Olatz San Sebastián Núria Garriga Gustavo A. Llorente 《Oecologia》2013,173(1):117-127
Food availability and pond desiccation are two of the most studied factors that condition amphibian metamorphosis. It is well known that, when food is abundant, organisms undergo metamorphosis early and when they are relatively large. The capability of anurans to accelerate their developmental rate in response to desiccation is also common knowledge. These two variables must act together in nature, since we know that, as a pond dries, the per capita resources decrease. We conduct an experiment to evaluate the effects of desiccation and food availability separately and in combination in tadpoles of the painted frog (Discoglossus pictus). We demonstrate that food deprivation leads to slow growth rates, which delay metamorphosis and produce smaller size and weight. The capability to accelerate metamorphosis when facing a drying pond is also confirmed, but, nevertheless, with factor interaction (when the pool is drying and resources are scarce) the capacity to respond to desiccation is lost. In addition, slow drying rates are shown to be stressful situations, but not enough to provoke a shortening of the larval period; in fact, the larval period becomes longer. We also demonstrate that the interaction of these factors changes the allometric relationship of different parts of the hind limb, which has implications for the biomechanics of jumping. Due to low mortality rates and an adequate response to both environmental factors, we expect D. pictus to have a great invasive potential in its new Mediterranean distribution area, where lots of temporary and ephemeral ponds are present. 相似文献
995.
Ma del Carmen Orozco-Mosqueda Crisanto Velázquez-Becerra Lourdes I. Macías-Rodríguez Gustavo Santoyo Idolina Flores-Cortez Ruth Alfaro-Cuevas Eduardo Valencia-Cantero 《Plant and Soil》2013,362(1-2):51-66
Background and aims
Iron is an essential nutrient for plant growth. Although abundant in soil, iron is poorly available. Therefore, plants have evolved mechanisms for iron mobilization and uptake from the rhizospheric environment. In this study, we examined the physiological responses to iron deficiency in Medicago truncatula plants exposed to volatile organic compounds (VOCs) produced by Arthrobacter agilis UMCV2.Methods
The VOC profiles of the plant and bacterium were determined separately and during interaction assays using gas chromatography. M. truncatula plants exposed to A. agilis VOCs and pure dimethylhexadecylamine were transferred to conditions of iron deficiency, and parameters associated with iron nutritional status were measured.Results
The relative abundance of the bacterial VOC dimethylhexadecylamine increased 12-fold when in co-cultures of A. agilis and M. truncatula, compared to axenic cultures. Plants exposed to bacterial VOCs or dimethylhexadecylamine exhibited a higher rhizosphere acidification capacity, enhanced ferric reductase activity, higher biomass generation, and elevated chlorophyll and iron content relative to controls.Conclusions
The VOCs emitted by A. agilis UMCV2 induce iron acquisition mechanisms in vitro in the Strategy I plant M. truncatula. Dimethylhexadecylamine is the signal molecule responsible for producing the beneficial effects. 相似文献996.
Gustavo Ricardo Spinelli Cecilia Veggiani Aybar María Julia Dantur Juri Mercedes Lizarralde de Grosso Pablo Ignacio Marino 《Memórias do Instituto Oswaldo Cruz》2013,108(5):586-589
The following two new species of Culicoides from the
Argentinean Yungas are described, illustrated and placed to subgenus or species
group and compared with related congeners: Culicoides calchaqui
Spinelli & Veggiani Aybar and Culicoides willinki Spinelli
& Veggiani Aybar. Culicoides daedaloides Wirth &
Blanton is recorded for the first time for Argentina and Culicoides
pseudoheliconiae Felippe-Bauer is firstly mentioned from the
northwestern region of the country. 相似文献
997.
Luciene de Fátima Costa Torres Dayana Ribeiro Raphael Hirata Jr Luis Gustavo Carvalho Pacheco Monica Cristina Souza Louisy Sanches dos Santos Cíntia Silva dos Santos Mohammad Salah Mateus Matiuzzi da Costa Marcio Garcia Ribeiro Salah A Selim Vasco Ariston de Carvalho Azevedo Ana Luiza Mattos-Guaraldi 《Memórias do Instituto Oswaldo Cruz》2013,108(3):272-279
Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR) assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp), 16S rRNA (C. ulcerans and C. pseudotuberculosis), pld (C. pseudotuberculosis), dtxR (C. diphtheriae) and tox [diphtheria toxin (DT) ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species. 相似文献
998.
Gizele D. Garcia Gustavo B. Gregoracci Eidy de O. Santos Pedro M. Meirelles Genivaldo G. Z. Silva Rob Edwards Tomoo Sawabe Kazuyoshi Gotoh Shota Nakamura Tetsuya Iida Rodrigo L. de Moura Fabiano L. Thompson 《Microbial ecology》2013,65(4):1076-1086
Coral health is under threat throughout the world due to regional and global stressors. White plague disease (WP) is one of the most important threats affecting the major reef builder of the Abrolhos Bank in Brazil, the endemic coral Mussismilia braziliensis. We performed a metagenomic analysis of healthy and WP-affected M. braziliensis in order to determine the types of microbes associated with this coral species. We also optimized a protocol for DNA extraction from coral tissues. Our taxonomic analysis revealed Proteobacteria, Bacteroidetes, Firmicutes, Cyanobacteria, and Actinomycetes as the main groups in all healthy and WP-affected corals. Vibrionales, members of the Cytophaga–Flavobacterium–Bacteroides complex, Rickettsiales, and Neisseriales were more abundant in the WP-affected corals. Diseased corals also had more eukaryotic metagenomic sequences identified as Alveolata and Apicomplexa. Our results suggest that WP disease in M. braziliensis is caused by a polymicrobial consortium. 相似文献
999.
Stefan Zdraljevic Drew Wagner Kevin Cheng Laura Ruohonen Jussi J?ntti Merja Penttil? Orna Resnekov C. Gustavo Pesce 《Applied and environmental microbiology》2013,79(24):7569-7582
Organic acids derived from engineered microbes can replace fossil-derived chemicals in many applications. Fungal hosts are preferred for organic acid production because they tolerate lignocellulosic hydrolysates and low pH, allowing economic production and recovery of the free acid. However, cell death caused by cytosolic acidification constrains productivity. Cytosolic acidification affects cells asynchronously, suggesting that there is an underlying cell-to-cell heterogeneity in acid productivity and/or in resistance to toxicity. We used fluorescence microscopy to investigate the relationship between enzyme concentration, cytosolic pH, and viability at the single-cell level in Saccharomyces cerevisiae engineered to synthesize xylonic acid. We found that cultures producing xylonic acid accumulate cells with cytosolic pH below 5 (referred to here as “acidified”). Using live-cell time courses, we found that the probability of acidification was related to the initial levels of xylose dehydrogenase and sharply increased from 0.2 to 0.8 with just a 60% increase in enzyme abundance (Hill coefficient, >6). This “switch-like” relationship likely results from an enzyme level threshold above which the produced acid overwhelms the cell''s pH buffering capacity. Consistent with this hypothesis, we showed that expression of xylose dehydrogenase from a chromosomal locus yields ∼20 times fewer acidified cells and ∼2-fold more xylonic acid relative to expression of the enzyme from a plasmid with variable copy number. These results suggest that strategies that further reduce cell-to-cell heterogeneity in enzyme levels could result in additional gains in xylonic acid productivity. Our results demonstrate a generalizable approach that takes advantage of the cell-to-cell variation of a clonal population to uncover causal relationships in the toxicity of engineered pathways. 相似文献
1000.
Dan E. Vivas-Ruiz Gustavo A. Sandoval Julio Mendoza Rosalina R. Inga Silea Gontijo Michael Richardson Johannes A. Eble Armando Yarleque Eladio F. Sanchez 《Biochimie》2013
The thrombin-like enzyme from Bothrops barnetti named barnettobin was purified. We report some biochemical features of barnettobin including the complete amino acid sequence that was deduced from the cDNA. Snake venom serine proteases affect several steps of human hemostasis ranging from the blood coagulation cascade to platelet function. Barnettobin is a monomeric glycoprotein of 52 kDa as shown by reducing SDS-PAGE, and contains approx. 52% carbohydrate by mass which could be removed by N-glycosidase. The complete amino acid sequence was deduced from the cDNA sequence. Its sequence contains a single chain of 233 amino acid including three N-glycosylation sites. The sequence exhibits significant homology with those of mammalian serine proteases e.g. thrombin and with homologous TLEs. Its specific coagulant activity was 251.7 NIH thrombin units/mg, releasing fibrinopeptide A from human fibrinogen and showed defibrinogenating effect in mouse. Both coagulant and amidolytic activities were inhibited by PMSF. N-deglycosylation impaired its temperature and pH stability. Its cDNA sequence with 750 bp encodes a protein of 233 residues. Indications that carbohydrate moieties may play a role in the interaction with substrates are presented. Barnettobin is a new defibrinogenating agent which may provide an opportunity for the development of new types of anti-thrombotic drugs. 相似文献