全文获取类型
收费全文 | 1889篇 |
免费 | 142篇 |
国内免费 | 2篇 |
专业分类
2033篇 |
出版年
2022年 | 14篇 |
2021年 | 19篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 18篇 |
2017年 | 12篇 |
2016年 | 23篇 |
2015年 | 63篇 |
2014年 | 84篇 |
2013年 | 97篇 |
2012年 | 142篇 |
2011年 | 139篇 |
2010年 | 74篇 |
2009年 | 77篇 |
2008年 | 127篇 |
2007年 | 125篇 |
2006年 | 120篇 |
2005年 | 116篇 |
2004年 | 127篇 |
2003年 | 99篇 |
2002年 | 89篇 |
2001年 | 22篇 |
2000年 | 22篇 |
1999年 | 31篇 |
1998年 | 33篇 |
1997年 | 33篇 |
1996年 | 23篇 |
1995年 | 13篇 |
1994年 | 19篇 |
1993年 | 16篇 |
1992年 | 28篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 15篇 |
1988年 | 10篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1980年 | 7篇 |
1979年 | 12篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1974年 | 6篇 |
1973年 | 12篇 |
1972年 | 5篇 |
1971年 | 6篇 |
排序方式: 共有2033条查询结果,搜索用时 0 毫秒
61.
Félix-Faure Jim Gaillard Jérémie Descloux Stéphane Chanudet Vincent Poirel Alain Baudoin Jean-Marc Avrillier Jean-Noël Millery Annie Dambrine Etienne 《Ecosystems》2019,22(2):312-330
Ecosystems - When a water reservoir is created, the pre-existing soils and vegetation are flooded. Here, we took advantage of the complete emptying of the Sarrans Reservoir, which was flooded... 相似文献
62.
Jean-Marc Bielser Jakub Domaradzki Jonathan Souquet Hervé Broly Massimo Morbidelli 《Biotechnology progress》2019,35(3):e2790
Perfusion cell culture, confined traditionally to the production of fragile molecules, is currently gaining broader attention in the biomanufacturing of therapeutic proteins. The development of these processes is made difficult by the limited availability of appropriate scale-down models. This is due to the continuous operation that requires complex control and cell retention capacity. For example, the determination of an optimal perfusion and bleed rate for continuous cell culture is often performed in scale-down bioreactors and requires a substantial amount of time and effort. To increase the experimental throughput and decrease the required workload, a semi-continuous procedure, referred to as the VCDmax (viable cell density) approach, has been developed on the basis of shake tubes (ST) and deepwell plates (96-DWP). Its effectiveness has been demonstrated for 12 different CHO-K1-SV cell lines expressing an IgG1. Further, its reliability has been investigated through proper comparisons with perfusion runs in lab-scale bioreactors. It was found that the volumetric productivity and the CSPRmin (cell specific perfusion rate) determined using the ST and 96-DWP models were successfully (mostly within the experimental error) confirmed in lab-scale bioreactors, which then covered a significant scale-up from the half milliliter to the liter scale. These scale-down models are very useful to design and scale-up optimal bioreactor operating conditions as well as screening for different media and cell lines. 相似文献
63.
beta-Oxidation is a cyclic pathway involved in the degradation of lipids. In yeast, it occurs in peroxisomes and the first step is catalyzed by an acyl-CoA oxidase (Aoxp). The yeast Yarrowia lipolytica possesses several genes (POX) coding for Aoxps. This study is based on the factorial analysis of results obtained with the many POX derivative strains that have been constructed previously. The effect of interactions between Aoxps on the acyl-CoA oxidase (Aox) activity was important even at the second order. We then investigated the effect of Aox activity on growth and lactone production. Aox activity was correlated with acidification of the medium by cells and with cellular growth but not with lactone production, although Aox activity on short chains was inversely correlated with lactone accumulation. Due to the poor correlation between Aox activity and lactone production, the modeling of this parameter gave no satisfactory results but growth depending on Aox activity was modeled. 相似文献
64.
Various approaches have been developed to define conservation units for plant and animal species. In this study we combined
nuclear microsatellites (from a previous published study) and chloroplast microsatellites (assessed in the present study),
leaf and seed morphology traits and abiotic variables (climate and soil) to define evolutionary significant units (ESU) of
Santalum austrocaledonicum, a tree species growing in New Caledonia. Results for chloroplast microsatellites showed that the total population heterozygosity
was␣high, (H
cp = 0.84) but varied between islands. Differentiation was strong in the total population (F
stcp = 0.66) but also within the main island Grande Terre (F
stcp = 0.73) and within Iles Loyauté (F
stcp = 0.52), highlighting a limited gene flow between populations. These results confirmed those obtained with nuclear microsatellites.
The cluster analysis on molecular markers discriminated two main groups constituted by the populations of Grande Terre and
the populations of Iles Loyauté. A principal component analysis of leaf and seed morphology traits singled out the populations
of Iles Loyauté and the western populations of Grande Terre. Quantitative genetic analyses showed that the variation between
populations was under genetic control (broad sense heritability close to 80%). A high correlation between rainfall and morphological
traits suggested an impact of climate on this variation. The integration of these results allows to define two ESUs, one corresponding
to Grande Terre and Ile des Pins and the other the Iles Loyauté archipelago. This study stresses the need to restore some
populations of Grande Terre that are currently threatened by their small size. 相似文献
65.
Toillon RA Lagadec C Page A Chopin V Sautière PE Ricort JM Lemoine J Zhang M Hondermarck H Le Bourhis X 《Molecular & cellular proteomics : MCP》2007,6(7):1239-1247
Normal breast epithelial cells are known to exert an apoptotic effect on breast cancer cells, resulting in a potential paracrine inhibition of breast tumor development. In this study we purified and characterized the apoptosis-inducing factors secreted by normal breast epithelial cells. Conditioned medium was concentrated by ultrafiltration and separated on reverse phase Sep-Pak C18 and HPLC. The proapoptotic activity of eluted fractions was tested on MCF-7 breast cancer cells, and nano-LC-nano-ESI-MS/MS allowed the identification of insulin-like growth factor-binding protein-3 (IGFBP-3) and maspin as the proapoptotic factors produced by normal breast epithelial cells. Western blot analysis of conditioned media confirmed the specific secretion of IGFBP-3 and maspin by normal cells but not by breast cancer cells. Immunodepletion of IGFBP-3 and maspin completely abolished the normal cell-induced apoptosis of cancer cells, and recombinant proteins reproduced the effect of normal cell-conditioned medium on apoptosis of breast cancer cells. Together our results indicated that normal breast epithelial cells can induce apoptosis of breast cancer cells through IGFBP-3 and maspin. These findings provide a molecular hypothesis for the long observed inhibitory effect of normal surrounding cells on breast cancer development. 相似文献
66.
67.
Nicole C. Thunes Rachel A. Conrad Haitham H. Mohammed Yongtao Zhu Paul Barbier Jason P. Evenhuis David Perez-Pascual Jean-Marc Ghigo Ryan S. Lipscomb John R. Schneider Nan Li Devon H. Erbes Clayton Birkett Benjamin R. LaFrentz Timothy J. Welch Mark J. McBride 《Applied and environmental microbiology》2022,88(3)
68.
Ritabrata Dutta Karim Zouaoui Boudjeltia Christos Kotsalos Alexandre Rousseau Daniel Ribeiro de Sousa Jean-Marc Desmet Alain Van Meerhaeghe Antonietta Mira Bastien Chopard 《PLoS computational biology》2022,18(3)
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment. 相似文献
69.
Microbe-associated parthenogenesis (thelytoky) has been discovered in nineTrichogramma species, parasitoids of mainly lepidopteran eggs. Parthenogenetic and bisexual conspecifics co-occur in many field populations.
As an initial step to understand the dynamics of these two reproductive strategies we studied the effect of microbe-associated
parthenogenesis on fecundity. The fecundity of two parthenogenetic isofemale lines ofT. pretiosum and one ofT. deion was compared with bisexual lines derived from them by antibiotic treatment. In all three cases parthenogenetic females were
less fecund over their lifetime than bisexual females. Also, parthenogenetic females produced fewer daughters in two cases
and in one case a similar number of daughters as their respective bisexual counterparts. The lack of mating and insemination
was excluded as an explanation for the reduced fecundity of parthenogenetic females, because mated and virgin parthenogenetic
females produce the same number of offspring. Antibiotic treatment can also be excluded because females of field-collected
bisexual line treated with antibiotics produced the same number of offspring as untreated females. The reduced fecundity of
parthenogenetic females was caused by a lower number of eggs being laid rather than by a greater developmental mortality.
Parthenogenetic females produced less daughters than bisexual females when host availability was not limiting, but when host
availability was severely limited, parthenogenetic females produced more daughters than the bisexual females. 相似文献
70.
G Protein β Subunit–null Mutants Are Impaired in Phagocytosis and Chemotaxis Due to Inappropriate Regulation of the Actin Cytoskeleton 下载免费PDF全文
Barbara Peracino Jane Borleis Tian Jin Monika Westphal Jean-Marc Schwartz Lijun Wu Enrico Bracco Günther Gerisch Peter Devreotes Salvatore Bozzaro 《The Journal of cell biology》1998,141(7):1529-1537
Chemotaxis and phagocytosis are basically similar in cells of the immune system and in Dictyostelium amebae. Deletion of the unique G protein β subunit in D. discoideum impaired phagocytosis but had little effect on fluid-phase endocytosis, cytokinesis, or random motility. Constitutive expression of wild-type β subunit restored phagocytosis and normal development. Chemoattractants released by cells or bacteria trigger typical transient actin polymerization responses in wild-type cells. In β subunit–null cells, and in a series of β subunit point mutants, these responses were impaired to a degree that correlated with the defect in phagocytosis. Image analysis of green fluorescent protein–actin transfected cells showed that β subunit– null cells were defective in reshaping the actin network into a phagocytic cup, and eventually a phagosome, in response to particle attachment. Our results indicate that signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis, suggesting the possible involvement of these effectors in the process. 相似文献