全文获取类型
收费全文 | 4872篇 |
免费 | 397篇 |
国内免费 | 3篇 |
专业分类
5272篇 |
出版年
2024年 | 5篇 |
2023年 | 31篇 |
2022年 | 99篇 |
2021年 | 150篇 |
2020年 | 83篇 |
2019年 | 97篇 |
2018年 | 105篇 |
2017年 | 94篇 |
2016年 | 185篇 |
2015年 | 293篇 |
2014年 | 329篇 |
2013年 | 363篇 |
2012年 | 459篇 |
2011年 | 403篇 |
2010年 | 275篇 |
2009年 | 231篇 |
2008年 | 306篇 |
2007年 | 304篇 |
2006年 | 269篇 |
2005年 | 232篇 |
2004年 | 222篇 |
2003年 | 242篇 |
2002年 | 193篇 |
2001年 | 28篇 |
2000年 | 19篇 |
1999年 | 34篇 |
1998年 | 43篇 |
1997年 | 26篇 |
1996年 | 26篇 |
1995年 | 19篇 |
1994年 | 14篇 |
1993年 | 18篇 |
1992年 | 18篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 6篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1958年 | 2篇 |
1934年 | 1篇 |
1932年 | 1篇 |
1931年 | 2篇 |
1929年 | 1篇 |
1928年 | 1篇 |
排序方式: 共有5272条查询结果,搜索用时 15 毫秒
111.
Direct intracranial, FMRI, and lesion evidence for the causal role of left inferotemporal cortex in reading 总被引:8,自引:0,他引:8
Gaillard R Naccache L Pinel P Clémenceau S Volle E Hasboun D Dupont S Baulac M Dehaene S Adam C Cohen L 《Neuron》2006,50(2):191-204
Models of the "visual word form system" postulate that a left occipitotemporal region implements the automatic visual word recognition required for efficient reading. This theory was assessed in a patient in whom reading was explored with behavioral measures, fMRI, and intracranial local field potentials. Prior to surgery, when reading was normal, fMRI revealed a normal mosaic of ventral visual selectivity for words, faces, houses, and tools. Intracranial recordings demonstrated that the left occipitotemporal cortex responded with a short latency to conscious but also to subliminal words. Surgery removed a small portion of word-responsive occipitotemporal cortex overlapping with the word-specific fMRI activation. The patient developed a marked reading deficit, while recognition of other visual categories remained intact. Furthermore, in the post-surgery fMRI map of visual cortex, only word-specific activations disappeared. Altogether, these results provide direct evidence for the causal role of the left occipitotemporal cortex in the recognition of visual words. 相似文献
112.
Andr Gomes-dos-Santos Manuel Lopes-Lima Andr M Machado Antnio Marcos Ramos Ana Usi Ivan N Bolotov Ilya V Vikhrev Sophie Breton L Filipe C Castro Rute R da Fonseca Juergen Geist Martin E
sterling Vincent Pri Amílcar Teixeira Han Ming Gan Oleg Simakov Elsa Froufe 《DNA research》2021,28(2)
Since historical times, the inherent human fascination with pearls turned the freshwater pearl mussel Margaritifera margaritifera (Linnaeus, 1758) into a highly valuable cultural and economic resource. Although pearl harvesting in M. margaritifera is nowadays residual, other human threats have aggravated the species conservation status, especially in Europe. This mussel presents a myriad of rare biological features, e.g. high longevity coupled with low senescence and Doubly Uniparental Inheritance of mitochondrial DNA, for which the underlying molecular mechanisms are poorly known. Here, the first draft genome assembly of M. margaritifera was produced using a combination of Illumina Paired-end and Mate-pair approaches. The genome assembly was 2.4 Gb long, possessing 105,185 scaffolds and a scaffold N50 length of 288,726 bp. The ab initio gene prediction allowed the identification of 35,119 protein-coding genes. This genome represents an essential resource for studying this species’ unique biological and evolutionary features and ultimately will help to develop new tools to promote its conservation. 相似文献
113.
Bich-Tram Huynh Elsa Kermorvant-Duchemin Rattanak Chheang Frederique Randrianirina Abdoulaye Seck Elisoa Hariniaina Ratsima Zafitsara Zo Andrianirina Jean-Baptiste Diouf Armya Youssouf Abdou Sophie Goyet Vronique Ngo Siyin Lach Long Pring Touch Sok Michael Padget Fatoumata Diene Sarr Laurence Borand Benoit Garin Jean-Marc Collard Perlinot Herindrainy Agathe de Lauzanne Muriel Vray Elisabeth Delarocque-Astagneau Didier Guillemot On behalf of the BIRDY study group 《PLoS medicine》2021,18(9)
BackgroundSevere bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries (LMICs). However, most data came from hospitals, which do not include neonates who did not seek care or were treated outside the hospital. Studies from the community are scarce, and few among those available were conducted with high-quality microbiological techniques. The burden of SBI at the community level is therefore largely unknown. We aimed here to describe the incidence, etiology, risk factors, and antibiotic resistance profiles of community-acquired neonatal SBI in 3 LMICs.Methods and findingsThe BIRDY study is a prospective multicentric community-based mother and child cohort study and was conducted in both urban and rural areas in Madagascar (2012 to 2018), Cambodia (2014 to 2018), and Senegal (2014 to 2018). All pregnant women within a geographically defined population were identified and enrolled. Their neonates were actively followed from birth to 28 days to document all episodes of SBI. A total of 3,858 pregnant women (2,273 (58.9%) in Madagascar, 814 (21.1%) in Cambodia, and 771 (20.0%) in Senegal) were enrolled in the study, and, of these, 31.2% were primigravidae. Women enrolled in the urban sites represented 39.6% (900/2,273), 45.5% (370/814), and 61.9% (477/771), and those enrolled in the rural sites represented 60.4% (1,373/2,273), 54.5% (444/814), and 38.1% (294/771) of the total in Madagascar, Cambodia, and Senegal, respectively. Among the 3,688 recruited newborns, 49.6% were male and 8.7% were low birth weight (LBW). The incidence of possible severe bacterial infection (pSBI; clinical diagnosis based on WHO guidelines of the Integrated Management of Childhood Illness) was 196.3 [95% confidence interval (CI) 176.5 to 218.2], 110.1 [88.3 to 137.3], and 78.3 [59.5 to 103] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively. The incidence of pSBI differed between urban and rural sites in all study countries. In Madagascar, we estimated an incidence of 161.0 pSBI per 1,000 live births [133.5 to 194] in the urban site and 219.0 [192.6 to 249.1] pSBI per 1,000 live births in the rural site (p = 0.008). In Cambodia, estimated incidences were 141.1 [105.4 to 189.0] and 85.3 [61.0 to 119.4] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.025), while in Senegal, we estimated 103.6 [76.0 to 141.2] pSBI and 41.5 [23.0 to 75.0] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.006). The incidences of culture-confirmed SBI were 15.2 [10.6 to 21.8], 6.5 [2.7 to 15.6], and 10.2 [4.8 to 21.3] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively, with no difference between urban and rural sites in each country. The great majority of early-onset infections occurred during the first 3 days of life (72.7%). The 3 main pathogens isolated were Klebsiella spp. (11/45, 24.4%), Escherichia coli (10/45, 22.2%), and Staphylococcus spp. (11/45, 24.4%). Among the 13 gram-positive isolates, 5 were resistant to gentamicin, and, among the 29 gram-negative isolates, 13 were resistant to gentamicin, with only 1 E. coli out of 10 sensitive to ampicillin. Almost one-third of the isolates were resistant to both first-line drugs recommended for the management of neonatal sepsis (ampicillin and gentamicin). Overall, 38 deaths occurred among neonates with SBI (possible and culture-confirmed SBI together). LBW and foul-smelling amniotic fluid at delivery were common risk factors for early pSBI in all 3 countries. A main limitation of the study was the lack of samples from a significant proportion of infants with pBSI including 35 neonatal deaths. Without these samples, bacterial infection and resistance profiles could not be confirmed.ConclusionsIn this study, we observed a high incidence of neonatal SBI, particularly in the first 3 days of life, in the community of 3 LMICs. The current treatment for the management of neonatal infection is hindered by antimicrobial resistance. Our findings suggest that microbiological diagnosis of SBI remains a challenge in these settings and support more research on causes of neonatal death and the implementation of early interventions (e.g., follow-up of at-risk newborns during the first days of life) to decrease the burden of neonatal SBI and associated mortality and help achieve Sustainable Development Goal 3.In a community-based, prospective cohort study, Bich-Tram Huynh and colleagues investigate the incidence and factors associated with several bacterial infections among neonates in rural and urban areas of three low-middle income countries. 相似文献
114.
Nathalie Deboosère Gaspard Deloison Samuel Jouny Anne‐Sophie Debrie Mathias Chamaillard Jérôme Nigou Martin Cohen‐Gonsaud Camille Locht Priscille Brodin Romain Veyron‐Churlet 《Cellular microbiology》2017,19(1)
Mycobacterium tuberculosis produces several bacterial effectors impacting the colonization of phagocytes. Here, we report that the putative lipoprotein LppM hinders phagocytosis by macrophages in a toll‐like receptor 2‐dependent manner. Moreover, recombinant LppM is able to functionally complement the phenotype of the mutant, when exogenously added during macrophage infection. LppM is also implicated in the phagosomal maturation, as a lppM deletion mutant is more easily addressed towards the acidified compartments of the macrophage than its isogenic parental strain. In addition, this mutant was affected in its ability to induce the secretion of pro‐inflammatory chemokines, interferon‐gamma‐inducible protein‐10, monocyte chemoattractant protein‐1 and macrophage inflammatory protein‐1α. Thus, our results describe a new mycobacterial protein involved in the early trafficking of the tubercle bacillus and its manipulation of the host immune response. 相似文献
115.
De Smedt-Peyrusse V Sargueil F Moranis A Harizi H Mongrand S Layé S 《Journal of neurochemistry》2008,105(2):296-307
Recognition of lipopolysaccharide (LPS), the endotoxin of gram-negative bacteria, by microglia occurs through its binding to specific receptors, cluster of differentiation 14 and toll-like receptor-4. LPS binding to these receptors triggers the synthesis of proinflammatory cytokines that coordinate the brain innate immune response to protect the CNS of the infection. Docosahexaenoic acid (DHA), a n -3 polyunsaturated fatty acid highly incorporated in the brain, is a potent immunomodulator. In this study, we investigated whether DHA modulates LPS receptor localization and, as a consequence, LPS-induced signaling pathway and proinflammatory cytokine production. We demonstrated that DHA, when added exogenously, is specifically enriched in membrane phospholipids, but not in raft lipids of microglial cells. DHA incorporation in membrane impaired surface presentation of LPS receptors cluster of differentiation 14 and toll-like receptor-4, but not their membrane subdomain localization. LPS-induced nuclear factor kappa B activation was inhibited by DHA, hence, LPS-induced proinflammatory cytokine synthesis of interleukin-1β and tumor necrosis factor α was strongly attenuated. We suggest that DHA is highly anti-inflammatory by targeting LPS receptor surface location, therefore reducing LPS action on microglia. This effect represents a new insight by which DHA modulates in the brain the expression of proinflammatory cytokines in response to bacterial product. 相似文献
116.
Sourrouille C Marquet-Blouin E D'Aoust MA Kiefer-Meyer MC Seveno M Pagny-Salehabadi S Bardor M Durambur G Lerouge P Vezina L Gomord V 《Plant biotechnology journal》2008,6(7):702-721
Compared with other plant expression systems used for pharmaceutical protein production, alfalfa offers the advantage of very homogeneous N -glycosylation. Therefore, this plant was selected for further attempts at glycoengineering. Two main approaches were developed in order to humanize N -glycosylation in alfalfa. The first was a knock-down of two plant-specific N -glycan maturation enzymes, β1,2-xylosyltransferase and α1,3-fucosyltransferases, using sense, antisense and RNA interference strategies. In a second approach, with the ultimate goal of rebuilding the whole human sialylation pathway, human β1,4-galactosyltransferase was expressed in alfalfa in a native form or in fusion with a targeting domain from N -acetylglucosaminyltransferase I, a glycosyltransferase located in the early Golgi apparatus in Nicotiana tabacum . Both knock-down and knock-in strategies strongly, but not completely, inhibited the biosynthesis of α1,3-fucose- and β1,2-xylose-containing glycoepitopes in transgenic alfalfa. However, recombinant human β1,4-galactosyltransferase activity in transgenic alfalfa completely prevented the accumulation of the Lewis a glycoepitope on complex N -glycans. 相似文献
117.
118.
Dufresne A Ostrowski M Scanlan DJ Garczarek L Mazard S Palenik BP Paulsen IT de Marsac NT Wincker P Dossat C Ferriera S Johnson J Post AF Hess WR Partensky F 《Genome biology》2008,9(5):R90-16
Background
The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this ecologically important group.Results
Here, we compare the genomes of 11 marine Synechococcus isolates, representing 10 distinct lineages. Phylogenies inferred from the core genome allowed us to refine the taxonomic relationships between clades by revealing a clear dichotomy within the main subcluster, reminiscent of the two aforementioned lifestyles. Genome size is strongly correlated with the cumulative lengths of hypervariable regions (or 'islands'). One of these, encompassing most genes encoding the light-harvesting phycobilisome rod complexes, is involved in adaptation to changes in light quality and has clearly been transferred between members of different Synechococcus lineages. Furthermore, we observed that two strains (RS9917 and WH5701) that have similar pigmentation and physiology have an unusually high number of genes in common, given their phylogenetic distance.Conclusion
We propose that while members of a given marine Synechococcus lineage may have the same broad geographical distribution, local niche occupancy is facilitated by lateral gene transfers, a process in which genomic islands play a key role as a repository for transferred genes. Our work also highlights the need for developing picocyanobacterial systematics based on genome-derived parameters combined with ecological and physiological data. 相似文献119.
120.
Sophie Martin Stéphanie Cohu Céline Vignot Guillaume Zimmerman Jean‐Pierre Gattuso 《Ecology and evolution》2013,3(3):676-693
The response of respiration, photosynthesis, and calcification to elevated pCO2 and temperature was investigated in isolation and in combination in the Mediterranean crustose coralline alga Lithophyllum cabiochae. Algae were maintained in aquaria during 1 year at near‐ambient conditions of irradiance, at ambient or elevated temperature (+3°C), and at ambient (ca. 400 μatm) or elevated pCO2 (ca. 700 μatm). Respiration, photosynthesis, and net calcification showed a strong seasonal pattern following the seasonal variations of temperature and irradiance, with higher rates in summer than in winter. Respiration was unaffected by pCO2 but showed a general trend of increase at elevated temperature at all seasons, except in summer under elevated pCO2. Conversely, photosynthesis was strongly affected by pCO2 with a decline under elevated pCO2 in summer, autumn, and winter. In particular, photosynthetic efficiency was reduced under elevated pCO2. Net calcification showed different responses depending on the season. In summer, net calcification increased with rising temperature under ambient pCO2 but decreased with rising temperature under elevated pCO2. Surprisingly, the highest rates in summer were found under elevated pCO2 and ambient temperature. In autumn, winter, and spring, net calcification exhibited a positive or no response at elevated temperature but was unaffected by pCO2. The rate of calcification of L. cabiochae was thus maintained or even enhanced under increased pCO2. However, there is likely a trade‐off with other physiological processes. For example, photosynthesis declines in response to increased pCO2 under ambient irradiance. The present study reports only on the physiological response of healthy specimens to ocean warming and acidification, however, these environmental changes may affect the vulnerability of coralline algae to other stresses such as pathogens and necroses that can cause major dissolution, which would have critical consequence for the sustainability of coralligenous habitats and the budgets of carbon and calcium carbonate in coastal Mediterranean ecosystems. 相似文献