全文获取类型
收费全文 | 3033篇 |
免费 | 252篇 |
国内免费 | 2篇 |
出版年
2023年 | 8篇 |
2022年 | 14篇 |
2021年 | 52篇 |
2020年 | 23篇 |
2019年 | 30篇 |
2018年 | 34篇 |
2017年 | 41篇 |
2016年 | 79篇 |
2015年 | 117篇 |
2014年 | 160篇 |
2013年 | 211篇 |
2012年 | 299篇 |
2011年 | 227篇 |
2010年 | 197篇 |
2009年 | 134篇 |
2008年 | 202篇 |
2007年 | 217篇 |
2006年 | 187篇 |
2005年 | 183篇 |
2004年 | 182篇 |
2003年 | 131篇 |
2002年 | 150篇 |
2001年 | 22篇 |
2000年 | 13篇 |
1999年 | 38篇 |
1998年 | 40篇 |
1997年 | 23篇 |
1996年 | 28篇 |
1995年 | 19篇 |
1994年 | 29篇 |
1993年 | 19篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 14篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 16篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1973年 | 10篇 |
1968年 | 4篇 |
排序方式: 共有3287条查询结果,搜索用时 15 毫秒
971.
Sergei I. Golovatch Jean-Jacques Geoffroy Pavel Stoev Didier?Vanden Spiegel 《ZooKeys》2013,(302):13-77
The small, basically Oriental family Opisotretidae is rediagnosed, reclassified, and shown to comprise the following seven genera, all keyed: Carlotretus Hoffman, 1980, with two species, including Carlotretus triramus
sp. n. from southern China; Corypholophus Attems, 1938, with two species, one in Vietnam, the other in the Ryukyus, Japan; Martensodesmus Golovatch, 1987, with eight species, all keyed, including Martensodesmus cattienensis
sp. n. from southern Vietnam, as well as Martensodesmus bedosae
sp. n. and Martensodesmus spiniger
sp. n. from southern China; Opisotretus Attems, 1907, with seven species, all keyed, including Opisotretus beroni
sp. n. and Opisotretus hagen
sp. n., both from Papua New Guinea, Opisotretus deharvengi
sp. n. from Sulawesi, Indonesia, and Opisotretus spinosus
sp. n. from Nusakambangan Island, off Java, Indonesia; Opisthoporodesmus Silvestri, 1899, with six nominate species; Retrodesmus Chamberlin, 1945, with two species, i.e. the type-species Retrodesmus dammermani Chamberlin, 1945, from Java, Indonesia, revised from the holotype, and Retrodesmus cavernicola
sp. n., from Papua New Guinea; and Solaenaulus Attems, 1940, with two species. Comments are presented on the family’s possible relationships and palaeogeographic history. Instead of being considered as the sole component of the superfamily Opisotretoidea, the Opisotretidae is believed here to form one of the families of the diverse superfamily Trichopolydesmoidea, perhaps the sister-group to, if not immediately derived from, the pantropical family Fuhrmannodesmidae. The origin of Opisotretidae, previously dated as far back as the Triassic (220 Ma) in relation to the fragmentation of eastern Gondwanaland, mainly in the region of present-day Indonesia, could have had nothing to do with Gondwanaland. Opisotretids might have originated in mainland Southeast Asia well within the Cenozoic, with subsequent dispersals along the Himalayas in the West and across Indonesia (including New Guinea) in the East, also reaching as far north as the Ryukyus, Japan and Guangxi, southern China. 相似文献
972.
Frédéric Le Manach Christian Chaboud Duncan Copeland Philippe Cury Didier Gascuel Kristin M. Kleisner André Standing U. Rashid Sumaila Dirk Zeller Daniel Pauly 《PloS one》2013,8(11)
The imperative to increase seafood supply while dealing with its overfished local stocks has pushed the European Union (EU) and its Member States to fish in the Exclusive Economic Zones of other countries through various types of fishing agreements for decades. Although European public fishing agreements are commented on regularly and considered to be transparent, this is the first global and historical study on the fee regime that governs them. We find that the EU has subsidized these agreements at an average of 75% of their cost (financial contribution agreed upon in the agreements), while private European business interests paid the equivalent of 1.5% of the value of the fish that was eventually landed. This raises questions of fisheries benefit-sharing and resource-use equity that the EU has the potential to address during the nearly completed reform of its Common Fisheries Policy. 相似文献
973.
Antoine Péré-Brissaud Xavier Blanchet Didier Delourme Patrick Pélissier Lionel Forestier Arnaud Delavaud Nathalie Duprat Brigitte Picard Abderrahman Maftah Laure Brémaud 《Open biology》2015,5(9)
α1-Antichymotrypsin is encoded by the unique SERPINA3 gene in humans, while it is encoded by a cluster of eight closely related genes in cattle. BovSERPINA3 proteins present a high degree of similarity and significant divergences in the reactive centre loop (RCL) domains which are responsible for the antiprotease activity. In this study, we analysed their expression patterns in a range of cattle tissues. Even if their expression is ubiquitous, we showed that the expression levels of each serpin vary in different tissues of 15-month-old Charolais bulls. Our results led us to focus on bovSERPINA3-7, one of the two most divergent members of the bovSERPINA3 family. Expression analyses showed that bovSERPINA3-7 protein presents different tissue-specific patterns with diverse degrees of N-glycosylation. Using a specific antibody raised against bovSERPINA3-7, Western blot analysis revealed a specific 96 kDa band in skeletal muscle. BovSERPINA3-7 immunoprecipitation and mass spectrometry revealed that this 96 kDa band corresponds to a complex of bovSERPINA3-7 and creatine kinase M-type. Finally, we reported that the bovSERPINA3-7 protein is present in slow-twitch skeletal myofibres. Precisely, bovSERPINA3-7 specifically colocalized with myomesin at the M-band region of sarcomeres where it could interact with other components such as creatine kinase M-type. This study opens new prospects on the bovSERPINA3-7 function in skeletal muscle and promotes opportunities for further understanding of the physiological role(s) of serpins. 相似文献
974.
Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43–3.13), 1.75 (1.50–2.03), 1.51 (1.05–2.17) and 1.91 (1.63–2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10–109) and €80 (€20–139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention. 相似文献
975.
IL-1 signaling for IL-2 production in T cells involves a rise in phosphatidylserine synthesis 总被引:4,自引:0,他引:4
M Didier C Aussel C Pelassy M Fehlmann 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(9):3078-3080
Activation of Jurkat T cells with anti-TCR, anti-CD3, anti-CD2, or PHA is accompanied by a strong inhibition of phosphatidylserine (PS) synthesis. The inhibition of the synthesis of this phospholipid could be partially reversed by IL-1. In Jurkat cells, IL-1 did not activate phosphodiesterases as demonstrated by the lack of change of inositol triphosphate and diacylglycerol levels as well as the lack of change in cytosolic Ca2+ concentration. Furthermore, IL-1 did not modify the intracellular level of cGMP and cAMP, suggesting that the observed rise of PS synthesis could play the role of mediator IL-1 action. As PS is a necessary cofactor for the activation of protein kinase C, our results suggest strongly that IL-1 modulate protein kinase C activity in the activated lymphocyte through its action on PS synthesis. 相似文献
976.
Covalent immobilization of pullulanase on alginate and study of its hydrolysis of pullulan
下载免费PDF全文
![点击此处可从《Biotechnology progress》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ghina Ali Virginie Dulong Sarah N. Gasmi Christophe Rihouey Luc Picton Didier Le Cerf 《Biotechnology progress》2015,31(4):883-889
The immobilization of pullulanase from Klebsiella pneumoniae by grafting was investigated. Pullulanase was linked after activation of alginate via a covalent bond between the amine groups of the enzyme and the carboxylic acid groups of alginate. The immobilization yield was 60%. The activity of free pullulanase and immobilized pullulanase was followed by the quantification of reducing ends by colorimetric assay and the determination of the molar masses of the hydrolyzed pullulan by SEC/MALS/DRI. Compared to free pullulanase, the kinetics is largely slowed. The evolution of the weight average molar mass of pullulan leading to high production of shorter oligosaccharides during hydrolysis is not the same as that obtained with free enzyme. Immobilized pullulanase retained 75% and 30% of its initial activity after 24 h and 14 days of incubation at 60°C, respectively while free pullulanase lost its activity after 5 h of hydrolysis at the same temperature. The kinetic parameters of immobilized pullulanase were also investigated by isothermal titration calorimetry (ITC). The affinity of immobilized enzyme to its substrate was reduced compared to the free pullulanase due to steric hindrance and chemical links. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:883–889, 2015 相似文献
977.
Background
Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix.Objective
We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.Methods
Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.Results
Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.Conclusion and Clinical Relevance
Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC. 相似文献978.
Marion Bougerol Frédéric Auradé Fran?ois M. Lambert Didier Le Ray Denis Combes Muriel Thoby-Brisson Frédéric Relaix Nicolas Pollet Hervé Tostivint 《PloS one》2015,10(2)
Xenopus is an excellent tetrapod model for studying normal and pathological motoneuron ontogeny due to its developmental morpho-physiological advantages. In mammals, the urotensin II-related peptide (UTS2B) gene is primarily expressed in motoneurons of the brainstem and the spinal cord. Here, we show that this expression pattern was conserved in Xenopus and established during the early embryonic development, starting at the early tailbud stage. In late tadpole stage, uts2b mRNA was detected both in the hindbrain and in the spinal cord. Spinal uts2b+ cells were identified as axial motoneurons. In adult, however, the uts2b expression was only detected in the hindbrain. We assessed the ability of the uts2b promoter to drive the expression of a fluorescent reporter in motoneurons by recombineering a green fluorescent protein (GFP) into a bacterial artificial chromosome (BAC) clone containing the entire X. tropicalis uts2b locus. After injection of this construction in one-cell stage embryos, a transient GFP expression was observed in the spinal cord of about a quarter of the resulting animals from the early tailbud stage and up to juveniles. The GFP expression pattern was globally consistent with that of the endogenous uts2b in the spinal cord but no fluorescence was observed in the brainstem. A combination of histological and electrophysiological approaches was employed to further characterize the GFP+ cells in the larvae. More than 98% of the GFP+ cells expressed choline acetyltransferase, while their projections were co-localized with α-bungarotoxin labeling. When tail myotomes were injected with rhodamine dextran amine crystals, numerous double-stained GFP+ cells were observed. In addition, intracellular electrophysiological recordings of GFP+ neurons revealed locomotion-related rhythmic discharge patterns during fictive swimming. Taken together our results provide evidence that uts2b is an appropriate driver to express reporter genes in larval motoneurons of the Xenopus spinal cord. 相似文献
979.
Ga?l Mourembou Florence Fenollar Jean Bernard Lekana-Douki Angelique Ndjoyi Mbiguino Sydney Maghendji Nzondo Pierre Blaise Matsiegui Rella Zoleko Manego Cyrille Herve Bile Ehounoud Fadi Bittar Didier Raoult Oleg Mediannikov 《PLoS neglected tropical diseases》2015,9(10)
Background
Like other tropical African countries, Gabon is afflicted by many parasitic diseases, including filariases such as loiasis and mansonellosis. This study aimed to assess the prevalence of these two filarial diseases in febrile and afebrile children using quantitative real-time PCR and standard PCR assays coupled with sequencing.Methodology/Principal Findings
DNA from blood specimens of 1,418 Gabonese children (1,258 febrile and 160 afebrile) were analyzed. Overall, filarial DNA was detected in 95 (6.7%) children, including 67 positive for M. perstans (4.7%), which was the most common. M. perstans was detected in 61/1,258 febrile children (4.8%) and 6/160 afebrile children (3.8%, P = 0.6). Its prevalence increased statistically with age: 3.5%, 7.7% and 10.6% in children aged ≤5, 6–10 and 11–15 years, respectively. M. perstans prevalence was significantly higher in Koulamoutou and Lastourville (12% and 10.5%, respectively) than in Franceville and Fougamou (2.6% and 2.4%, respectively). Loa loa was detected in seven febrile children including one co-infection with M. perstans. Finally, 21 filarial DNA positive were negative for M. perstans and Loa loa, but ITS sequencing could be performed for 12 and allowed the identification of a potential new species of Mansonella provisionally called “DEUX”. Mansonella sp. “DEUX” was detected only in febrile children.Conclusions/Significance
Further study should be performed to characterize Mansonella sp. “DEUX” and evaluate the clinical significance of mansonellosis in humans. 相似文献980.
Giorgia Urbinati Hafiz Muhammad Ali Quentin Rousseau Hubert Chapuis Didier Desma?le Patrick Couvreur Liliane Massaad-Massade 《PloS one》2015,10(5)
TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV), most frequently identified in patients’ biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67). In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene. 相似文献