全文获取类型
收费全文 | 1938篇 |
免费 | 131篇 |
国内免费 | 1篇 |
专业分类
2070篇 |
出版年
2023年 | 8篇 |
2022年 | 27篇 |
2021年 | 35篇 |
2020年 | 31篇 |
2019年 | 39篇 |
2018年 | 57篇 |
2017年 | 39篇 |
2016年 | 66篇 |
2015年 | 92篇 |
2014年 | 116篇 |
2013年 | 133篇 |
2012年 | 173篇 |
2011年 | 140篇 |
2010年 | 95篇 |
2009年 | 83篇 |
2008年 | 118篇 |
2007年 | 127篇 |
2006年 | 113篇 |
2005年 | 100篇 |
2004年 | 80篇 |
2003年 | 61篇 |
2002年 | 62篇 |
2001年 | 16篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 20篇 |
1997年 | 14篇 |
1996年 | 15篇 |
1995年 | 11篇 |
1994年 | 13篇 |
1993年 | 10篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 9篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1971年 | 5篇 |
1968年 | 5篇 |
1967年 | 6篇 |
排序方式: 共有2070条查询结果,搜索用时 0 毫秒
81.
82.
M. Florencia Breitman Luciano J. Avila Jack W. Sites Jr Mariana Morando 《Molecular ecology》2012,21(24):6068-6085
Patagonia was shaped by a complex geological history, including the Miocene uplift of the Andes, followed by volcanism, marine introgressions, and extreme climatic oscillations during Pliocene–Pleistocene glaciation–deglaciation cycles. The distributional patterns and phylogenetic relationships of southern patagonian animals and plants were affected in different ways, and those imprints are reflected in the seven phylogeographic breaks and eight refugia that have been previously proposed. In this study, we estimated time‐calibrated phylogenetic/phylogeographic patterns in lizards of the Liolaemus lineomaculatus group and relate them to historical Miocene‐to‐Pleistocene events of Patagonia and the previously proposed phylogeographic patterns. Individuals from 51 localities were sequenced for the mitochondrial marker (cyt‐b) and a subsample of individuals from each mitochondrial lineage was sequenced for one nuclear (LDA12D) and one slow evolving mitochondrial gene (12S). Our analyses revealed strong phylogeographic structure among lineages and, in most cases, no signal of demographic changes through time. The lineomaculatus group is composed of three strongly supported clades (lineomaculatus, hatcheri and kolengh + silvanae), and divergence estimates suggested their origins associated with the oldest known Patagonian glaciation (7–5 Ma); subsequent diversification within the lineomaculatus clade coincided with the large Pliocene glaciations (~3.5 Ma). The lineomaculatus clade includes nine strongly genetically and geographically structured lineages, five of which are interpreted as candidate species. Our findings suggest that some Liolaemus lineages have persisted in situ, each of them in a different refugium, through several glaciation–deglaciation cycles without demographic fluctuations. We also summarize and update qualitative evidence of some shared phylogeographic breaks and refugia among plants, rodents and lizards. 相似文献
83.
Lluis Morey Alexandra Santanach Luciano Di Croce 《Molecular and cellular biology》2015,35(16):2716-2728
Embryonic stem cells (ESCs) are characterized by their ability to self-renew and to differentiate into all cell types of a given organism. Understanding the molecular mechanisms that govern the ESC state is of great interest not only for basic research—for instance, ESCs represent a perfect system to study cellular differentiation in vitro—but also for their potential implications in human health, as these mechanisms are likewise involved in cancer progression and could be exploited in regenerative medicine. In this minireview, we focus on the latest insights into the molecular mechanisms mediated by the pluripotency factors as well as their roles during differentiation. We also discuss recent advances in understanding the function of the epigenetic regulators, Polycomb and MLL complexes, in ESC biology. 相似文献
84.
Elena Gabrielli Eva Pericolini Elio Cenci Federica Ortelli Walter Magliani Tecla Ciociola Francesco Bistoni Stefania Conti Anna Vecchiarelli Luciano Polonelli 《PloS one》2009,4(12)
Background
It has been documented that, independently from the specificity of the native antibody (Ab) for a given antigen (Ag), complementarity determining regions (CDR)-related peptides may display differential antimicrobial, antiviral and antitumor activities.Methodology/Principal Findings
In this study we demonstrate that a synthetic peptide with sequence identical to VHCDR3 of a mouse monoclonal Ab (mAb) specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i) proinflammatory cytokine production; ii) PI3K-Akt pathway and iii) TLR-4 expression. Significantly, VHCDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties.Conclusions/Significance
These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity. 相似文献85.
Seahorses (Syngnathidae: Hippocampus) are iconic marine teleosts that are readily identifiable by their upright posture. The fossil record is inadequate to shed light on the evolution of this trait because it lacks transitional forms. There are, however, extant syngnathid species (the pygmy pipehorses) that look like horizontally swimming seahorses and that might represent a surviving evolutionary link between the benthic seahorses and other, free-swimming members of the family Syngnathidae. Using sequence data from five nuclear loci, we confirm the sister taxon relationship between seahorses and pygmy pipehorses. Molecular dating indicates that the two taxa diverged during the Late Oligocene. During this time, tectonic events in the Indo-West Pacific resulted in the formation of vast amounts of new shallow-water areas and associated expansion of seagrass habitats that would have favoured the seahorses’ upright posture by improving their camouflage while not affecting their manoeuvrability negatively. The molecular techniques employed here provide new insights into the evolution of a taxon whose fossil record is incomplete, but whose evolutionary history is so recent that the major stages of morphological evolution are still represented in extant species. 相似文献
86.
Federica Susta Davide Chiasserini Katia Fettucciari Pier Luigi Orvietani Flavia Quotadamo Rosina Noce Andrea Bartoli Pierfrancesco Marconi Lanfranco Corazzi Luciano Binaglia 《Proteomics》2010,10(11):2099-2112
Protein expression changes induced in thioglycolate‐elicited peritoneal murine macrophages (MΦ) by infection with type III Group B Streptococcus (GBS) are described. Proteins from control MΦ and MΦ incubated 2 h with live or heat‐inactivated GBS were separated by 2‐DE. Proteins whose expression was significantly different in infected MΦ, as compared with control cells, were identified by MS/MS analysis. Changes in the expression level of proteins involved in both positive and negative modulation of phagocytic functions, stress response and cell death were induced in MΦ by GBS infection. In particular, expression of enzymes playing a key role in production of reactive oxygen species was lowered in GBS‐infected MΦ. Significant alterations in the expression of some metabolic enzymes were also observed, most of the glycolytic and of the pentose‐cycle enzymes being down‐regulated in MΦ infected with live GBS. Finally, evidence was obtained that GBS infection affects the expression of enzymes or enzyme subunits involved in ATP synthesis and in adenine nucleotides interconversion processes. 相似文献
87.
Background
Mutations in the integral membrane protein 2B [1], also known as BRI2 [2], a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia [3]. In these conditions, accumulation of a C-terminal peptide (ABri and ADan) cleaved off from the mutated precursor protein by the pro-protein convertase furin [4], leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer''s disease has lead to the finding that BRI2 interacts with the Amyloid Precursor Protein (APP), decreasing the efficiency of APP processing to generate Aβ [5], [6], [7]. The interaction between the two precursors, APP and BRI2, and possibly between Aβ and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate.Methodology/Principal Findings
We have generated the first BRI2 Danish Knock-In (FDDKI) murine model of FDD, expressing the pathogenic decamer duplication in exon 6 of the BRI2 gene. FDDKI mice do not show any evident abnormal phenotype, with normal brain histology and no detectable amyloid deposition in blood vessel walls or parenchyma.Conclusions/Significance
This new murine mouse model will be important to further understand the interaction between APP and BRI2, and to provide insights into the molecular basis of FDD. 相似文献88.
Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria 总被引:22,自引:1,他引:22 下载免费PDF全文
The cell wall envelopes of gram-positive bacteria represent a surface organelle that not only functions as a cytoskeletal element but also promotes interactions between bacteria and their environment. Cell wall peptidoglycan is covalently and noncovalently decorated with teichoic acids, polysaccharides, and proteins. The sum of these molecular decorations provides bacterial envelopes with species- and strain-specific properties that are ultimately responsible for bacterial virulence, interactions with host immune systems, and the development of disease symptoms or successful outcomes of infections. Surface proteins typically carry two topogenic sequences, i.e., N-terminal signal peptides and C-terminal sorting signals. Sortases catalyze a transpeptidation reaction by first cleaving a surface protein substrate at the cell wall sorting signal. The resulting acyl enzyme intermediates between sortases and their substrates are then resolved by the nucleophilic attack of amino groups, typically provided by the cell wall cross bridges of peptidoglycan precursors. The surface protein linked to peptidoglycan is then incorporated into the envelope and displayed on the microbial surface. This review focuses on the mechanisms of surface protein anchoring to the cell wall envelope by sortases and the role that these enzymes play in bacterial physiology and pathogenesis. 相似文献
89.
Production of an Engineered Killer Peptide in Nicotiana benthamiana by Using a Potato virus X Expression System 总被引:1,自引:0,他引:1 下载免费PDF全文
Marcello Donini Chiara Lico Selene Baschieri Stefania Conti Walter Magliani Luciano Polonelli Eugenio Benvenuto 《Applied microbiology》2005,71(10):6360-6367
The decapeptide killer peptide (KP) derived from the sequence of a single-chain, anti-idiotypic antibody acting as a functional internal image of a microbicidal, broad-spectrum yeast killer toxin (KT) was shown to exert a strong microbicidal activity against human pathogens. With the aim to exploit this peptide to confer resistance to plant pathogens, we assayed its antimicrobial activity against a broad spectrum of phytopathogenic bacteria and fungi. Synthetic KP exhibited antimicrobial activity in vitro towards Pseudomonas syringae, Erwinia carotovora, Botrytis cinerea, and Fusarium oxysporum. KP was also expressed in plants by using a Potato virus X (PVX)-derived vector as a fusion to the viral coat protein, yielding chimeric virus particles (CVPs) displaying the heterologous peptide. Purified CVPs showed enhanced antimicrobial activity against the above-mentioned plant pathogens and human pathogens such as Staphylococcus aureus and Candida albicans. Moreover, in vivo assays designed to challenge KP-expressing plants (as CVPs) with Pseudomonas syringae pv. tabaci showed enhanced resistance to bacterial attack. The results indicate that the PVX-based display system is a high-yield, rapid, and efficient method to produce and evaluate antimicrobial peptides in plants, representing a milestone for the large-scale production of high-added-value peptides through molecular farming. Moreover, KP is a promising molecule to be stably engineered in plants to confer broad-spectrum resistance to phytopathogens. 相似文献