全文获取类型
收费全文 | 183篇 |
免费 | 21篇 |
国内免费 | 3篇 |
专业分类
207篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 11篇 |
2014年 | 8篇 |
2013年 | 12篇 |
2012年 | 12篇 |
2011年 | 12篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 6篇 |
2005年 | 9篇 |
2004年 | 11篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1968年 | 1篇 |
1964年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有207条查询结果,搜索用时 15 毫秒
101.
Borrero J Brede DA Skaugen M Diep DB Herranz C Nes IF Cintas LM Hernández PE 《Applied and environmental microbiology》2011,77(1):369-373
Lactococcus garvieae DCC43 produces a bacteriocin, garvicin ML (GarML), with a molecular mass of 6,004.2 Da. Data from de novo amino acid sequencing by tandem mass spectrometry and nucleotide sequencing by reverse genetics suggested that the bacteriocin is synthesized as a 63-amino-acid precursor with a 3-amino-acid leader peptide that is removed by cleavage. Subsequently, a covalent linkage between the N and C termini forms the mature version of this novel 60-amino-acid circular bacteriocin. 相似文献
102.
BARBARA RANDLKOFER ELISABETH OBERMAIER JÉRÔME CASAS TORSTEN MEINERS 《Ecological Entomology》2010,35(4):446-455
1. A heterogeneous habitat structure can have a profound impact on foraging carnivorous arthropods. In the present study, we examined which elements of complex vegetation structure influence the searching movement of a parasitoid model organism. 2. Previous field work showed that tall and dense vegetation reduces the parasitism success of the eulophid egg parasitoid Oomyzus galerucivorus while the probability of host egg deposition increased close to plant tips. 3. In laboratory bioassays, dried grass stems were arranged according to the natural situation in different setups. The wasps' walking time on stems increased with increasing stem height and density. High stem density decreased the walking time of the parasitoids on the ground and an increased stem height reduced the propensity to fly to the ground. Connectivity had a minor positive effect on the number of stem contacts, but considerably reduced the number of wasps reaching the upper part of grass stems by two‐thirds. 4. Thus, although enhanced vegetation complexity enhances walking activity of the parasitoids in the vegetation, laying eggs at the tip of long grass stems in dense vegetation can be an adaptive strategy for the host, as it maximises the number of connections between plant parts to cross by parasitoids before reaching the host. The connection points disorient the wasps, which lose time, reverse their direction or fly away. 相似文献
103.
Karen Silence Torsten Dreier Mahan Moshir Peter Ulrichts Sofie ME Gabriels Michael Saunders Harald Wajant Peter Brouckaert Leander Huyghe Tim Van Hauwermeiren Alain Thibault Hans J De Haard 《MABS-AUSTIN》2014,6(2):523-532
Overexpression of CD70 has been documented in a variety of solid and hematological tumors, where it is thought to play a role in tumor proliferation and evasion of immune surveillance. Here, we describe ARGX-110, a defucosylated IgG1 monoclonal antibody (mAb) that selectively targets and neutralizes CD70, the ligand of CD27.
ARGX-110 was generated by immunization of outbred llamas. The antibody was germlined to 95% human identity, and its anti-tumor efficacy was tested in several in vitro assays. ARGX-110 binds CD70 with picomolar affinity. In depletion studies, ARGX-110 lyses tumor cells with greater efficacy than its fucosylated version. In addition, ARGX-110 demonstrates strong complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis activity. ARGX-110 inhibits signaling of CD27, which results in blocking of the activation and proliferation of Tregs. In a Raji xenograft model, administration of the fucosylated version of ARGX-110 resulted in a prolonged survival at doses of 0.1 mg/kg and above. The pharmacokinetics of ARGX-110 was tested in cynomolgus monkeys; the calculated half-life is 12 days.
In conclusion, ARGX-110 is a potent blocking mAb with a dual mode of action against both CD70-bearing tumor cells and CD70-dependent Tregs. This antibody is now in a Phase 1 study in patients with advanced malignancies expressing CD70 (). NCT01813539相似文献
104.
Wenling E Chang Keri Sarver Brandon W Higgs Timothy D Read Nichole ME Nolan Carol E Chapman Kimberly A Bishop-Lilly Shanmuga Sozhamannan 《BMC bioinformatics》2011,12(1):109
Background
OmniLog™ phenotype microarrays (PMs) have the capability to measure and compare the growth responses of biological samples upon exposure to hundreds of growth conditions such as different metabolites and antibiotics over a time course of hours to days. In order to manage the large amount of data produced from the OmniLog™ instrument, PheMaDB (Phenotype Microarray DataBase), a web-based relational database, was designed. PheMaDB enables efficient storage, retrieval and rapid analysis of the OmniLog™ PM data. 相似文献105.
Simone S. Riedel Anja Mottok Christian Brede Carina A. B?uerlein Ana-Laura Jordán Garrote Miriam Ritz Katharina Mattenheimer Andreas Rosenwald Hermann Einsele Bjarne Bogen Andreas Beilhack 《PloS one》2012,7(12)
Background
Multiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.Material and Methods
A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Results
Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.Conclusions
This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring the effects of different treatment regimens. 相似文献106.
We describe here a computational morphology-based approach to the investigation of possible causes of chromatin alterations in sperm. A comprehensive set of state-of-the-art and geometric measures are computationally extracted from toluidine blue stained images and analyzed to infer the possible processes leading to normal and abnormal chromatin formation while seeking a possible taxonomy of chromatin alterations and their influence on sperm head morphology. Using this methodology, we have identified higher chromatin fragility at some specific points of the sperm head. Despite the lack of correlation between morphologies of sperm head and chromatin structure, four main morphological types of chromatin alterations in bull spermatozoa have been identified and their possible causes discussed. 相似文献
107.
YOHAN PILLON† JÉRÔME MUNZINGER HAMID AMIR† HELEN C. F. HOPKINS‡ MARK W. CHASE§ 《Molecular ecology》2009,18(10):2263-2275
We reconstructed the evolutionary history of Codia , a plant genus endemic to the New Caledonia biodiversity hotspot in the southwest Pacific, using three single-copy nuclear genes. It seems likely that more than half of Codia species have a hybrid origin, but in the absence of cytological information, it is not known whether polyploids occur. Adaptation to ultramafic soils is possibly a plesiomorphic character for the entire genus. We found that species of hybrid origin can have some morphological characters absent in putative parental species, that is, they exhibit transgressive phenotypes. There is evidence of considerable range alteration post-origin in several species because some likely parental species of hybrid taxa no longer co-occur and are confined to putative rainforest refugia; in some cases, hybrid species do not now co-occur with either of their parental species. These results have implications for the design of conservation strategies, for example, prioritization of parental species for ex-situ conservation and preservation of the contact zones between soil types where hybridization is more likely to occur (i.e. conserving the possibility for the process to continue rather than trying to conserve taxa). 相似文献
108.
THOMAS BROQUET JONATHAN YEARSLEY ALEXANDRE H. HIRZEL JÉRÔME GOUDET NICOLAS PERRIN 《Molecular ecology》2009,18(6):1048-1060
We present a novel and straightforward method for estimating recent migration rates between discrete populations using multilocus genotype data. The approach builds upon a two-step sampling design, where individual genotypes are sampled before and after dispersal. We develop a model that estimates all pairwise backwards migration rates ( mij , the probability that an individual sampled in population i is a migrant from population j ) between a set of populations. The method is validated with simulated data and compared with the methods of BayesAss and Structure. First, we use data for an island model and then we consider more realistic data simulations for a metapopulation of the greater white-toothed shrew ( Crocidura russula ). We show that the precision and bias of estimates primarily depend upon the proportion of individuals sampled in each population. Weak sampling designs may particularly affect the quality of the coverage provided by 95% highest posterior density intervals. We further show that it is relatively insensitive to the number of loci sampled and the overall strength of genetic structure. The method can easily be extended and makes fewer assumptions about the underlying demographic and genetic processes than currently available methods. It allows backwards migration rates to be estimated across a wide range of realistic conditions. 相似文献
109.
JULIEN FOUCAUD JÉRÔME ORIVEL DENIS FOURNIER JACQUES H. C. DELABIE ANNE LOISEAU JULIEN LE BRETON PHILIPPE CERDAN ARNAUD ESTOUP 《Molecular ecology》2009,18(24):5059-5073
The invasive ant species Wasmannia auropunctata displays both ecologically dominant and non‐dominant populations within its native range. Three factors could theoretically explain the ecological dominance of some native populations of W. auropunctata: (i) its clonal reproductive system, through demographic and/or adaptive advantages; (ii) its unicolonial social organization, through lower intraspecific and efficient interspecific competition; (iii) the human disturbance of its native range, through the modification of biotic and abiotic environmental conditions. We used microsatellite markers and behavioural tests to uncover the reproductive modes and social organization of dominant and non‐dominant native populations in natural and human‐modified habitats. Microsatellite and mtDNA data indicated that dominant and non‐dominant native populations (supercolonies as determined by aggression tests) of W. auropunctata did not belong to different evolutionary units. We found that the reproductive system and the social organization are neither necessary nor sufficient to explain W. auropunctata ecological dominance. Dominance rather seems to be set off by unknown ecological factors altered by human activities, as all dominant populations were recorded in human‐modified habitats. The clonal reproductive system found in some populations of W. auropunctata may however indirectly contribute to its ecological dominance by allowing the species to expand its environmental niche, through the fixation over time of specific combinations of divergent male and female genotypes. Unicoloniality may rather promote the range expansion of already dominant populations than actually trigger ecological dominance. The W. auropunctata model illustrates the strong impact of human disturbance on species’ ecological features and the adaptive potential of clonal reproductive systems. 相似文献
110.