全文获取类型
收费全文 | 2546篇 |
免费 | 204篇 |
国内免费 | 1篇 |
出版年
2022年 | 23篇 |
2021年 | 44篇 |
2020年 | 24篇 |
2019年 | 33篇 |
2018年 | 42篇 |
2017年 | 32篇 |
2016年 | 58篇 |
2015年 | 149篇 |
2014年 | 120篇 |
2013年 | 211篇 |
2012年 | 209篇 |
2011年 | 214篇 |
2010年 | 115篇 |
2009年 | 115篇 |
2008年 | 144篇 |
2007年 | 196篇 |
2006年 | 156篇 |
2005年 | 134篇 |
2004年 | 122篇 |
2003年 | 121篇 |
2002年 | 111篇 |
2001年 | 19篇 |
2000年 | 9篇 |
1999年 | 28篇 |
1998年 | 32篇 |
1997年 | 25篇 |
1996年 | 21篇 |
1995年 | 16篇 |
1994年 | 24篇 |
1993年 | 19篇 |
1992年 | 7篇 |
1991年 | 13篇 |
1990年 | 10篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 8篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1950年 | 3篇 |
1943年 | 3篇 |
1937年 | 3篇 |
排序方式: 共有2751条查询结果,搜索用时 95 毫秒
181.
Florence Cliquet Evelyne Picard-Meyer Miroslav Mojzis Zuzana Dirbakova Zita Muizniece Ingrida Jaceviciene Franco Mutinelli Marta Matulova Jitka Frolichova Ivan Rychlik Vladimir Celer 《PloS one》2015,10(10)
Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release. 相似文献
182.
183.
Didier K. Ekouévi Véronique Avettand-Fèno?l Boris K. Tchounga Patrick A. Coffie Adrien Sawadogo Daouda Minta Albert Minga Serge P. Eholie Jean-Christophe Plantier Florence Damond Fran?ois Dabis Christine Rouzioux IeDEA West Africa collaboration 《PloS one》2015,10(6)
Background
Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.Method
A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL).Results
A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (<10 cps/mL), it was detectable between 10-100 cps/mL in 35.8%, between 100-1000 cps/mL in 11.7% and >1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL.Conclusion
This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment. 相似文献184.
Atika Meklat Noureddine Bouras Amar Riba Abdelghani Zitouni Florence Mathieu Manfred Rohde Peter Schumann Cathrin Spröer Hans-Peter Klenk Nasserdine Sabaou 《Antonie van Leeuwenhoek》2014,106(2):287-292
A halophilic actinomycete strain, designated H27T, was isolated from a soil sample collected from a hypersaline habitat in Djelfa Province (North-Central Algeria), and then investigated using a polyphasic taxonomic approach. The strain was observed to produce poor aerial mycelium, which formed short chains of oval to cylindrical-shaped spores at maturity, and non fragmented substrate mycelium. The optimum NaCl concentration for growth was found to be 10–15 % (w/v) and the optimum growth temperature and pH were found to be 28–37 °C and 6–7, respectively. The diagnostic diamino acid in the cell-wall peptidoglycan was identified as meso-diaminopimelic acid. The predominant menaquinones of strain H27T were identified as MK-11 (H4) and MK-10 (H6). The major fatty acids were found to be iso-C16:0, anteiso-C17:0, 10 methyl C17:0 and 10 methyl C16:0. The diagnostic phospholipids detected were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylinositol. The chemotaxonomic properties of strain H27T are consistent with those shared by members of the genus Streptomonospora. 16S rRNA gene sequence analysis indicated that strain H27T is most closely related to Streptomonospora alba DSM 44588T (98.8 %) and Streptomonospora flavalba DSM 45155T (98.7 %) whereas the DNA–DNA relatedness values between strain H27T and the two type strains were 17.1 and 57.9 %, respectively. Based on the combined genotypic and phenotypic evidence, it is proposed that strain H27T should be classified as representative of a novel species, for which the name Streptomonospora algeriensis sp. nov. is proposed. The type strain is H27T (=DSM 45604T =CCUG 63369T =MTCC 11563T). 相似文献
185.
186.
Abigail Perez-Valdespino Yunfeng Li Barbara Setlow Sonali Ghosh David Pan George Korza Florence E. Feeherry Christopher J. Doona Yong-Qing Li Bing Hao Peter Setlow 《Journal of bacteriology》2014,196(11):2077-2088
The Bacillus subtilis
spoVAEa and spoVAF genes are expressed in developing spores as members of the spoVA operon, which encodes proteins essential for the uptake and release of dipicolinic acid (DPA) during spore formation and germination. SpoVAF is likely an integral inner spore membrane protein and exhibits sequence identity to A subunits of the spore''s nutrient germinant receptors (GRs), while SpoVAEa is a soluble protein with no obvious signals to allow its passage across a membrane. However, like SpoVAD, SpoVAEa is present on the outer surface of the spore''s inner membrane, as SpoVAEa was accessible to an external biotinylation agent in spores and SpoVAEa disappeared in parallel with SpoVAD during proteinase K treatment of germinated spores. SpoVAEa and SpoVAD were also distributed similarly in fractions of disrupted dormant spores. Unlike spoVAD, spoVAEa is absent from the genomes of some spore-forming members of the Bacillales and Clostridiales orders, although SpoVAEa''s amino acid sequence is conserved in species containing spoVAEa. B. subtilis strains lacking SpoVAF or SpoVAEa and SpoVAF sporulated normally, and the spores had normal DPA levels. Spores lacking SpoVAF or SpoVAEa and SpoVAF also germinated normally with non-GR-dependent germinants but more slowly than wild-type spores with GR-dependent germinants, and this germination defect was complemented by ectopic expression of the missing proteins. 相似文献
187.
188.
Nicolas Szabo-Fresnais Florence Lefebvre Aurore Germain Rodolphe Fischmeister Martine Pomérance 《Cellular signalling》2010,22(7):1143-1152
The sympathetic nervous system and pro-inflammatory cytokines play key roles in numerous cardiovascular disorders. Chronic β-adrenergic receptor (β-AR) stimulation in myocardium induces expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), which contribute to cardiac hypertrophy and failure. To evaluate the relationship between β-AR stimulation and pro-inflammatory cytokines, we studied the effects of the β-AR agonist isoprenaline (ISO) on IL-1-induced IL-6 production in adult rat ventricular myocytes (ARVMs). We report that ISO and IL-1 synergistically enhanced IL-6 gene expression and secretion. The synergistic effect of ISO was mimicked by cAMP elevating agents and involved the Gs protein/cAMP/PKA signalling pathway, but not the exchange factor EPAC. To evaluate the contribution of IL-6 to cellular hypertrophy, we examined the signalling pathways stimulated by the membrane-bound IL-6 receptor (IL-6R), and the IL-6 soluble receptor (sIL-6R) involved in the mechanism named IL-6 trans-signalling. The IL-6/sIL-6R complex promoted a rapid and persistent phosphorylation of STAT3Tyr705 in ARVMs. Moreover, IL-6 trans-signalling increased protein synthesis, c-fos gene expression and B-type natriuretic peptide secretion, three markers of cardiac hypertrophy. IL-6 trans-signalling also increased cell size. In contrast, IL-6 alone had no significant effect on either cell size or STAT3 phosphorylation although it induced phosphorylation of ERK1/2, AKT and S6K, demonstrating the presence of a functional IL-6R in ARVMs. Taken together, these results demonstrate that β-AR stimulation synergises with IL-1 for IL-6 secretion in adult ventricular myocytes and indicate that IL-6 induces cardiac hypertrophy only via IL-6 trans-signalling. The IL-6 soluble receptor may thus serve as a switch for IL-6 to activate STAT3 phosphorylation and hypertrophy. 相似文献
189.
Facchiano Francesco Deloye Florence Doussau Frédéric Innamorati Giulio Ashton Anthony C. Dolly J. Oliver Beninati Simone Facchiano Angelo Luini Alberto Poulain Bernard Benfenati Fabio 《Amino acids》2010,38(1):257-262
The aim of this study was to collect evidences on the role of transglutaminase (TG, E.C.2.3.2.13) in the antineoplastic properties
exerted by nimesulide (NMS), a non-steroidal anti-inflammatory drug, on murine B16-F10 melanoma cells. Treatment of melanoma
cells with nimesulide produces a considerable reduction of cell proliferation, paralleled by a remarkable decrease of the
intracellular concentration of polyamines spermidine and spermine. NMS treatment induces cancer cell differentiation, likely
through the observed enhancement of TG and tyrosinase activities and increase of melanin production, well known markers of
melanocyte differentiation. The overall results highlight the possibility that nimesulide acts as antineoplastic agent likely
through the induction of intracellular TG activity. 相似文献
190.
Daniel Ambort Florence Brellier Christoph Becker-Pauly Walter Stöcker Snezana Andrejevic-Blant Matthias Chiquet Erwin E. Sterchi 《Matrix biology》2010,29(1):31-42
The metalloprotease meprin has been implicated in tissue remodelling due to its capability to degrade extracellular matrix components. Here, we investigated the susceptibility of tenascin-C to cleavage by meprinβ and the functional properties of its proteolytic fragments. A set of monoclonal antibodies against chicken and human tenascin-C allowed the mapping of proteolytic fragments generated by meprinβ. In chicken tenascin-C, meprinβ processed all three major splicing variants by removal of 10 kDa N-terminal and 38 kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern was found for large human tenascin-C variant where two N-terminal peptides (10 or 15 kDa) and two C-terminal fragments (40 and 55 kDa) were removed from the intact subunit. N-terminal sequencing revealed the exact amino acid positions of cleavage sites. In both chicken and human tenascin-C N-terminal cleavages occurred just before and/or after the heptad repeats involved in subunit oligomerization. In the human protein, an additional cleavage site was identified in the alternative fibronectin type III repeat D. Whereas all these sites are known to be attacked by several other proteases, a unique cleavage by meprinβ was located to the 7th constant fibronectin type III repeat in both chicken and human tenascin-C, thereby removing the C-terminal domain involved in its anti-adhesive activity. In cell adhesion assays meprinβ-digested human tenascin-C was not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Whereas the expression of meprinβ and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibited many meprinβ-positive leukocytes in regions where tenascin-C was strongly induced. Our data indicate that, at least under pathological conditions, meprinβ might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity. 相似文献