全文获取类型
收费全文 | 716篇 |
免费 | 17篇 |
专业分类
733篇 |
出版年
2024年 | 12篇 |
2023年 | 14篇 |
2022年 | 18篇 |
2021年 | 43篇 |
2020年 | 20篇 |
2019年 | 22篇 |
2018年 | 23篇 |
2017年 | 10篇 |
2016年 | 30篇 |
2015年 | 44篇 |
2014年 | 37篇 |
2013年 | 48篇 |
2012年 | 76篇 |
2011年 | 48篇 |
2010年 | 27篇 |
2009年 | 35篇 |
2008年 | 39篇 |
2007年 | 25篇 |
2006年 | 35篇 |
2005年 | 24篇 |
2004年 | 17篇 |
2003年 | 25篇 |
2002年 | 17篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1974年 | 2篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有733条查询结果,搜索用时 15 毫秒
1.
Migratory bird species have smaller brains than non-migratory species. The behavioural flexibility/migratory precursor hypothesis suggests that sedentary birds have larger brains to allow the behavioural flexibility required in a seasonally variable habitat. The energy trade-off hypothesis proposes that brains are heavy, energetically expensive and therefore, incompatible with migration. Here, we compared relative brain, neocortex and hippocampus volume between migratory and sedentary bats at the species-level and using phylogenetically independent contrasts. We found that migratory bats had relatively smaller brains and neocortices than sedentary species. Our results support the energy trade-off hypothesis because bats do not exhibit the same degree of flexibility in diet selection as sedentary birds. Our results also suggest that bat brain size differences are subtler than those found in birds, perhaps owing to bats'' shorter migration distances. Conversely, we found no difference in relative hippocampus volume between migratory and sedentary species, underscoring our limited understanding of the role of the hippocampus in bats. 相似文献
2.
Cell expansion in roots 总被引:7,自引:0,他引:7
Cell expansion in roots is crucial for the exploration and exploitation of the soil substrate and the plethora of activities that roots engage in. Expansion requires the coordinated activities of many cell processes. Central to this is the control of ion transport during vacuolar growth, which mediates the increase in cell size and the concomitant production of new wall and membrane at the surface of growing cells. The cytoskeleton plays an important role in growth and the control of growth direction. Evidence is accumulating to show that plant hormones also coordinate cell expansion throughout the plant by controlling the activities of growth-regulating DELLA proteins. 相似文献
3.
4.
Vidne M Ahmadian Y Shlens J Pillow JW Kulkarni J Litke AM Chichilnisky EJ Simoncelli E Paninski L 《Journal of computational neuroscience》2012,33(1):97-121
Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations. 相似文献
5.
The rickettsial bacterium Ehrlichia ruminantium is the causative agent of heartwater, a serious tick-borne disease in ruminants. The genetic diversity of organisms in the field will have implications for cross-protective capacities of any vaccine developed, and for an effective vaccine design strategy proper genotyping and understanding of existing genetic diversity in the field is necessary. We searched for variable-number tandem-repeat (VNTR) loci for use in a multi-locus VNTR analysis (MLVA). Sequencing analysis of 30 potential VNTRs using a panel of 17 reference strains from geographically diverse origins identified 12 VNTRs with allelic profiles differing between strains. Application of MLVA to 38 E. ruminantium-infected Amblyomma variegatum collected from indigenous cattle in 6 different districts of Uganda identified 21 MLVA types. The discriminatory power of MLVA was greater than that of map1 PCR-restriction fragment length polymorphism analysis, with which only 6 genotypes were obtained. The high discriminatory power as well as cost- effective performance of MLVA provide the potential for this technique to be applied in the future with respect to optimizing vaccine trials by identifying local strain diversity, and also raise the possibility of exploring the association between E. ruminantium genotypes and phenotypes such as pathological outcome in the ruminant host. 相似文献
6.
Stephanie Holst Kathrin Stavenhagen Crina I. A. Balog Carolien A. M. Koeleman Liam M. McDonnell Oleg A. Mayboroda Aswin Verhoeven Wilma E. Mesker Rob A. E. M. Tollenaar André M. Deelder Manfred Wuhrer 《Molecular & cellular proteomics : MCP》2013,12(11):3081-3093
Cancer is a leading cause of death and alterations of glycosylation are characteristic features of malignant cells. Colorectal cancer is one of the most common cancers and its exact causes and biology are not yet well understood. Here, we compared glycosylation profiles of colorectal tumor tissues and corresponding control tissues of 13 colorectal cancer patients to contribute to the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC-MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled glycans from glycosphingolipids. Multivariate data analysis revealed significant differences between tumor and corresponding control tissues. Main discriminators were obtained, which represent the overall alteration in glycosylation of glycosphingolipids during colorectal cancer progression, and these were found to be characterized by (1) increased fucosylation, (2) decreased acetylation, (3) decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5) disialyl gangliosides. The findings of our current research confirm former reports, and in addition expand the knowledge of glycosphingolipid glycosylation in colorectal cancer by revealing new glycans with discriminative power and characteristic, cancer-associated glycosylation alterations. The obtained discriminating glycans can contribute to progress the discovery of biomarkers to improve diagnostics and patient treatment.Worldwide, cancer is a leading cause of death. With estimated 1.2 million diagnoses in 2008, colorectal cancer is the third most common cancer in the world and the fourth most common cause of death with an annual mortality of ∼600 000 (1). The exact causes of colorectal cancer are unknown, but different risk factors such as age, polyps, personal and family history, ulcerative colitis, or Crohn''s colitis have been proposed (2). Standard screening procedures include flexible sigmoidoscopy, colonoscopy, and immunological fecal occult blood testing. Each of them has its advantages and drawbacks such as invasiveness or low sensitivity and specificity (3). The method of choice for the treatment of colorectal cancer is surgery and therapeutic decisions are based on the tumor, lymph node, and metastasis staging-system as a prognostic factor (4). Current research has led to improved treatment strategies of colorectal cancer, however, the clinical outcome, the progression of the disease, and the response to the treatment remain variable among individuals. The heterogeneity of colorectal cancer at the molecular level—caused by accumulation of multiple genetic changes—may be one of the main reasons for this variability (5). Genetic factors such as instabilities, but also expression levels (6) can explain part of the cancer biology, but glycomics is gaining importance to complement the overall picture as aberrant glycosylation of proteins and lipids has been shown to be correlated with disease and malignancy (7, 8).Glycosylation is involved in many biological processes and especially its functional role in cellular interaction with respect to adhesion, cell growth, and signaling is prone to be affected in cancer progression, invasion, and metastasis (9). Several cancer-associated alterations in protein glycosylation have been reported: (1) increased branching of N-glycans, (2) higher density of O-glycans, and (3) incomplete synthesis of glycans. More particularly, an increased or induced expression of GlcNAc transferase V resulting in N-glycan structures with β1–6GlcNAc antennae (5, 10), and the expression of (sialyl) Tn-antigens (11) as aberrant O-glycosylation have been reported (10).Altered glycosphingolipid (GSL)1 glycosylation of the cell surface membrane during malignancy can affect cell recognition, adhesion, and signal transduction (12) and is found to reflect: (1) incomplete synthesis with or without precursor accumulation, (2) neosynthesis (9), (3) increased sialylation, and (4) increased fucosylation (13). In many cancers, including colorectal cancer, an overexpression of the (sialyl) Lewis X antigen (10, 14) and the expression of (sialyl) Lewis A (15) are considered to be related to malignant transformation—reflecting incomplete synthesis of sialyl 6-sulfo Lewis X and disialyl Lewis A (16) as well as neosynthesis (17). Studies on gangliosides showed an overexpression of these sialylated GSLs in human malignant melanoma (18). Furthermore, the involvement of gangliosides in cell adhesion and motility was reported, which contributes to tumor metastasis (19). Specifically, the gangliosides GD3 (Hex2NeuAc2ceramide) and GM2 (Hex2HexNAc1NeuAc1ceramide) have been found to be associated with tumor-angiogenesis (19). The up-regulation of fucosyltransferases in cancer was shown to cause a higher degree of fucosylation in malignant tissues (20) and Moriwaki et al. proposed that the increase in the fucosylation for GSLs was an early event in cancer (21). Misonou et al. investigated glycans derived from GSLs in colorectal cancer tissues showing aberrant glycan structures based on linkage differences as well as increased sialylation and fucosylation compared with control tissue (22), which is in line with observed changes in GSL glycosylation with regard to cancer progression (9, 13).Recently, we investigated the N-glycosylation profiles of colorectal tumors and correlating control tissues for biomarker discovery. Statistical analyses revealed an increase of sulfated glycan structures as well as paucimannosidic glycans and glycans containing sialylated Lewis type epitopes in the tumor tissue, whereas structures with bisecting GlcNAc were found to be decreased in malignancy (23). To further progress the understanding of colorectal cancer biology and the improvement of diagnostic tools and patient treatment, we complemented this recent study on N-glycosylation by an investigation of the glycosphingolipid-derived glycans (named GSL-glycans in the following) from frozen tumor tissues and corresponding control tissues from the same 13 colorectal cancer patients. GSL-glycans were enzymatically released, labeled with 2-aminobenzoic acid (AA) and analyzed by hydrophilic interaction liquid chromatography (HILIC) with fluorescence detection as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Employing multivariate statistical analysis, this approach revealed an intricate GSL-glycosylation pattern of tumor tissues and specific glycosylation differences in comparison to the corresponding control tissue. 相似文献
7.
Christof Junkes Axel Wessolowski Sebastien Farnaud Robert W Evans Liam Good Michael Bienert Margitta Dathe 《Journal of peptide science》2008,14(4):535-543
Cyclization of R- and W-rich hexapeptides has been found to enhance specifically the antimicrobial activity against Gram-negative Escherichia coli. To gain insight into the role of the bacterial outer membrane in mediating selectivity, we assayed the activity of cyclic hexapeptides derived from the parent sequence c-(RRWWRF) against several E. coli strains and Bacillus subtilis, L-form bacteria, and E. coli lipopolysaccharide (LPS) mutant strains, and we also investigated the peptide-induced permeabilization of the outer and inner membrane of E. coli. Wall-deficient L-form bacteria were distinctly less susceptible than the wild type strain. The patterns of peptide-induced permeabilization of the outer and inner E. coli membranes correlated well with the antimicrobial activity, confirming that membrane permeabilization is a detrimental effect of the peptides upon bacteria. Truncation of LPS had no influence on the activity of the cyclic parent peptide, but the highly active c-(RRWFWR), with three adjacent aromatic residues, required the complete LPS for maximal activity. Furthermore, differences in the activity of the parent peptide and its all-D sequence indicated stereospecific interactions with the LPS mutant strains. We suggest that, depending on the primary sequence of the peptides, either hydrophobic interactions with the fatty acid chains of lipid A, or electrostatic interactions disturbing the polar core region and interference with saccharide-saccharide interactions prevail in the barrier-disturbing effect upon the outer membrane and thereby provide peptide accessibility to the inner membrane. The results underline the importance of tryptophan and arginine residues and their relative location for a high antimicrobial effect, and the activity-modulating function of the outer membrane of E. coli. In addition to membrane permeabilization, the data provided evidence for the involvement of other mechanisms in growth inhibition and killing of bacteria. 相似文献
8.
Lorna I. Harris David Olefeldt Nicolas Pelletier Christian Blodau Klaus-Holger Knorr Julie Talbot Liam Heffernan Merritt Turetsky 《Global Change Biology》2023,29(19):5720-5735
Rapid, ongoing permafrost thaw of peatlands in the discontinuous permafrost zone is exposing a globally significant store of soil carbon (C) to microbial processes. Mineralization and release of this peat C to the atmosphere as greenhouse gases is a potentially important feedback to climate change. Here we investigated the effects of permafrost thaw on peat C at a peatland complex in western Canada. We collected 15 complete peat cores (between 2.7 and 4.5 m deep) along four chronosequences, from elevated permafrost peat plateaus to saturated thermokarst bogs that thawed up to 600 years ago. The peat cores were analysed for peat C storage and peat quality, as indicated by decomposition proxies (FTIR and C/N ratios) and potential decomposability using a 200-day aerobic laboratory incubation. Our results suggest net C loss following thaw, with average total peat C stocks decreasing by ~19.3 ± 7.2 kg C m−2 over <600 years (~13% loss). Average post-thaw accumulation of new peat at the surface over the same period was ~13.1 ± 2.5 kg C m−2. We estimate ~19% (±5.8%) of deep peat (>40 cm below surface) C is lost following thaw (average 26 ± 7.9 kg C m−2 over <600 years). Our FTIR analysis shows peat below the thaw transition in thermokarst bogs is slightly more decomposed than peat of a similar type and age in permafrost plateaus, but we found no significant changes to the quality or lability of deeper peat across the chronosequences. Our incubation results also showed no increase in C mineralization of deep peat across the chronosequences. While these limited changes in peat quality in deeper peat following permafrost thaw highlight uncertainty in the exact mechanisms and processes for C loss, our analysis of peat C stocks shows large C losses following permafrost thaw in peatlands in western Canada. 相似文献
9.
We have cloned and expressed the putative Caenorhabditis elegans orthologue for small glutamine-rich tetratricopeptide repeat-containing protein, now assigned the gene name sgt-1 in the C. elegans genome database. Characterization of the purified protein by cross-linking, mass spectrometry and gel filtration experiments provides unambiguous evidence that SGT-1 forms homo-dimers in solution. The hydrodynamic dimensions of SGT-1 dimers in relation to their molecular weight suggest a protein with a low level of compactness and an extended conformation. Human SGT has been shown to interact with and regulate the activity of heat shock proteins Hsp70 and Hsp90 via a TPR domain mediated interaction. The SGT TPR domain (SGT-1-TPR, residues 100-226) was cloned, purified and shown by ITC and CD analysis to interact with the C-terminal peptides of Hsp70 and Hsp90 with comparable affinities although there is no evidence of a recently proposed coupled binding-folding mechanism for TPR domains. 相似文献
10.