全文获取类型
收费全文 | 7307篇 |
免费 | 570篇 |
国内免费 | 1篇 |
专业分类
7878篇 |
出版年
2023年 | 57篇 |
2022年 | 107篇 |
2021年 | 222篇 |
2020年 | 141篇 |
2019年 | 153篇 |
2018年 | 172篇 |
2017年 | 152篇 |
2016年 | 252篇 |
2015年 | 421篇 |
2014年 | 445篇 |
2013年 | 527篇 |
2012年 | 675篇 |
2011年 | 635篇 |
2010年 | 391篇 |
2009年 | 359篇 |
2008年 | 499篇 |
2007年 | 424篇 |
2006年 | 413篇 |
2005年 | 351篇 |
2004年 | 310篇 |
2003年 | 245篇 |
2002年 | 260篇 |
2001年 | 47篇 |
2000年 | 42篇 |
1999年 | 50篇 |
1998年 | 43篇 |
1997年 | 36篇 |
1996年 | 32篇 |
1995年 | 34篇 |
1994年 | 28篇 |
1993年 | 17篇 |
1992年 | 39篇 |
1991年 | 29篇 |
1990年 | 21篇 |
1989年 | 27篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 21篇 |
1985年 | 19篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1973年 | 9篇 |
排序方式: 共有7878条查询结果,搜索用时 0 毫秒
991.
992.
Nicolas Larranaga Michel Baguette Olivier Calvez Delphine Legrand 《Insect Science》2019,26(4):743-752
When, how often and for how long organisms mate can have strong consequences for individual fitness and are crucial aspects of evolutionary ecology. Such determinants are likely to be of even greater importance in monandrous species and species with short adult life stages. Previous work suggests that mobility, a key dispersal? related trait, may affect the dynamics of copulations, but few studies have investigated the impact of individual mobility on mating latency, copulation duration and oviposition latency simultaneously. In this paper, we monitored the copulation dynamics of 40 males and 40 females, as well as the oviposition dynamics of the females of the Large White butterfly Pieris brassicae, a facultative long-distance disperser butterfly. Individuals from a breeding were selected to create a uniform distribution of mobility and we recorded the timing, number and duration of all copulations in a semiexperimental system. We showed that mobility, measured as the time spent in flight under stressful conditions (a proxy of dispersal tendency), correlates with all aspects of copulation dynamics: mobile males and females mated earlier and for shorter periods than less mobile individuals. In turn, late mating females increased the time between copulation and oviposition. These results feed the previously described mobility syndrome of R brassicae, involving morphological and physiological characters, with life-history traits. We suggest that the reduction of mating latency and copulation duration has an adaptive value in dispersing individuals, as their life expectancy might be shorter than that of sedentary individuals. 相似文献
993.
ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells 下载免费PDF全文
Valentina Chiusolo Guillaume Jacquemin Emma Boydell Sebastian Zamorano Cristina Riccadonna Serena Pellegatta Nicolas Hulo Valérie Dutoit Madiha Derouazi Pierre Yves Dietrich Paul R Walker Denis Martinvalet 《The EMBO journal》2017,36(11):1493-1512
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem‐like cells (GSC) being more sensitive to cytotoxic lymphocyte‐mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to GDCs. Forced ER–mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER–mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. 相似文献
994.
El Amri C Lacombe C Zimmerman K Ladram A Amiche M Nicolas P Bruston F 《Biochemistry》2006,45(48):14285-14297
The present study investigates the relationships between structural polymorphism, adsorption onto membrane mimetic support, lipid disturbance, and biological activity of bactericidal 23-residue, glycine-leucine-rich dermaseptin orthologues from the Phyllomedusinae frog skin, the "plasticins". Biological activities were evaluated using the membrane models DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) for prokaryotic membranes and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine) for eukaryotic membranes. We performed a conformational analysis of plasticins by molecular simulations and spectroscopic methods and analyzed phospholipid perturbations by infrared spectroscopy. Adsorption onto synthetic model membranes was quantified by surface plasmon resonance. Biological assays including antimicrobial and membrane potential-dissipating activities, together with hemolytic tests and imaging analysis of cytotoxicity, were carried out to clarify the peptide-membrane interactions. Two major groups were distinguished: (i) Neutral plasticins revealed the presence of strong beta-structures with the zwitterionic or anionic phospholipid vesicles. They were weakly adsorbed in the range of antibacterial activity concentrations (micromolar). Nevertheless, for millimolar concentrations, they caused perturbations at the interface peptide-DMPG vesicles and in the bilayer alkyl chains, suggesting insertion into bacterial membranes. (ii) Cationic plasticins revealed multiple conformational transitions, including destabilized helix states, beta-structures, and disordered states. Peptide-lipid complex densities depended on hydrophobic bond strengths. The most soluble cationic plasticins were strongly adsorbed, with stable peptide-lipid interactions inducing noticeable perturbations of bilayer alkyl chains, pointing out possible insertion into bacterial membranes. In contrast, cytotoxic plasticins were less adsorbed, with less stable peptide-lipid interactions causing membrane dehydration, formation of peptide-membrane hydrogen bonds, and little disturbances of lipid alkyl chains. These characteristics could be compatible with their putative action on intracellular targets leading to apoptosis. 相似文献
995.
Background
Microsporidia are intracellular parasites that are highly-derived relatives of fungi. They have compacted genomes and, despite a high rate of sequence evolution, distantly related species can share high levels of gene order conservation. To date, only two species have been analysed in detail, and data from one of these largely consists of short genomic fragments. It is therefore difficult to determine how conservation has been maintained through microsporidian evolution, and impossible to identify whether certain regions are more prone to genomic stasis.Principal Findings
Here, we analyse three large fragments of the Enterocytozoon bieneusi genome (in total 429 kbp), a species of medical significance. A total of 296 ORFs were identified, annotated and their context compared with Encephalitozoon cuniculi and Antonospora locustae. Overall, a high degree of conservation was found between all three species, and interestingly the level of conservation was similar in all three pairwise comparisons, despite the fact that A. locustae is more distantly related to E. cuniculi and E. bieneusi than either are to each other.Conclusions/Significance
Any two genes that are found together in any pair of genomes are more likely to be conserved in the third genome as well, suggesting that a core of genes tends to be conserved across the entire group. The mechanisms of rearrangments identified among microsporidian genomes were consistent with a very slow evolution of their architecture, as opposed to the very rapid sequence evolution reported for these parasites. 相似文献996.
Apoptotic death concurrent with CD3 stimulation in primary human CD8+ T lymphocytes: a role for endogenous granzyme B 总被引:1,自引:0,他引:1
Laforge M Bidère N Carmona S Devocelle A Charpentier B Senik A 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(7):3966-3977
We exposed primary CD8(+) T cells to soluble CD3 mAb plus IL-2 and limited numbers of monocytes (3%). These cells were activated but concurrently subjected to ongoing apoptosis ( approximately 25% were apoptotic from day 2 of culture). However, their costimulated CD4(+) counterparts were much less prone to apoptosis. The apoptotic signaling pathway bypassed Fas and TNFRs, and required the activity of cathepsin C, a protease which performs the proteolytic maturation of granzyme (Gr) A and GrB proenzymes within the cytolytic granules. Silencing the GrB gene by RNA interference in activated CD8(+) T cells prevented the activation of procaspase-3 and Bid, and indicated that GrB was the upstream death mediator. A GrB-specific mAb immunoprecipitated a approximately 70-kDa molecular complex from cytolytic extracts of activated CD8(+) (but not resting) T cells, that was specifically recognized by a nucleocytoplasmic protease inhibitor 9 (PI-9) specific mAb. This complex was also detected after reciprocal immunoprecipitation of PI-9. It coexisted in the cytosol with the 32-kDa form of GrB. As neither were detected in the cytosol of CD4(+) bystander T cells (which poorly synthesized GrB), and as silencing the perforin (Pf) gene had no effect in our system, endogenous GrB was likely implicated. Immunoprecipitation experiments failed to reveal Pf in the cytosol of CD8(+) T cells, and only a tiny efflux of granular GrA was detected by ELISA. We propose that some GrB is released from cytolytic granules to the cytosol of CD8(+) T lymphocytes upon CD3/TCR stimulation and escapes PI-9, thereby mediating apoptotic cell death. 相似文献
997.
Nicolas Robin 《Journal of the history of biology》2011,44(2):283-304
This paper demonstrates the importance of the reception and development of Goethe’s metamorphosis of plants as a methodological
and philosophical framework in the history of botanical theories. It proposes a focus on the textbooks written by the German
botanist Ludwig Reichenbach and his first attempt to use Goethe’s idea of metamorphosis of plants as fundamental to his natural
system of plants published under the title ‘Botany for Women’, in German Botanik für Damen (1828). In this book, Reichenbach paid particular attention to Goethe’s sensitive views on the essence of nature; he regarded Goethe’s
idea of metamorphosis in the plant kingdom as an ideal model to interpret connections of natural phenomena, in particular
as a conceptual frame for a natural system. Furthermore, he aimed to develop the philosophical statement of the metamorphosis,
in which he called for nature-philosophical conceptions in order to materialize his representation of plant “affinities,”
and of a kind of “ontogeny” of the whole plant kingdom. This paper demonstrates that, between speculative views and empirical
attempts, the extent to which Reichenbach actually belonged to a new “school” of thought, which left its mark on the history
and philosophy of botany. 相似文献
998.
999.
A key point in the study of acoustic perception is whether brain responsiveness to sounds depends on sound acoustic structure or sound perceptive salience. Songbirds provide some evidence that higher auditory regions are sensitive to the subjective importance of the stimulus for the subject. In the present paper, we compare brain activation elicited by mate versus non-mate calls in female zebra finches Taeniopygia guttata. Using playback, we examined the responsiveness of the caudal telencephalon by measuring the evoked expression of the immediate early gene ZENK. Our results show that mate calls elicit a significantly higher ZENK expression than the calls of another male in hippocampus, but not in auditory areas. Using a hierarchical ascending classification, we show that this difference in brain activation is not explained by call acoustic structure, but relies on call identity. Thus, these results give evidence for a genomic response to calls in hippocampus that differentiate between call identity, and not between call structure. Our study gives further insight into the implication of the hippocampus in sound recognition in female songbirds. 相似文献
1000.
Peiyu Liu Yan Liu Xiang Zhao Andrew P. Roberts Heng Zhang Yue Zheng Fuxian Wang Lushan Wang Nicolas Menguy Yongxin Pan Jinhua Li 《Environmental microbiology》2021,23(2):1115-1129
Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB. 相似文献