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101.
Sreeman K. Mamidyala Soumya Ramu Johnny X. Huang Avril A.B. Robertson Matthew A. Cooper 《Bioorganic & medicinal chemistry letters》2013,23(6):1667-1670
Anacardic acid derivatives exhibit a broad range of biological activities. In this report, an efficient method for the synthesis of anacardic acid derivatives was explored, and a small set of salicylic acid variants synthesised retaining a constant hydrophobic element (a naphthyl tail). The naphthyl side chain was introduced via Wittig reaction and the aldehyde installed using directed ortho-metalation reaction of the substituted o-anisic acids. The failure of ortho-metalation using unprotected carboxylic acid group compelled us to use directed ortho-metalation in which a tertiary amide was used as a strong ortho-directing group. In the initial route, tertiary amide cleavage during final step was challenging, but cleaving the tertiary amide before Wittig reaction was beneficial. The Wittig reaction with protected carboxylic group (methyl ester) resulted in side-products whereas using sodium salt resulted in higher yields. The novel compounds were screened for antibacterial activity and cytotoxicity. Although substitution on the salicylic head group enhanced antibacterial activities they also enhanced cytotoxicity. 相似文献
102.
David T.W. Fei William F. Graham John G. McDougal Bruce A. Scoggins John P. Coghlan 《Life sciences》1980,27(16):1495-1502
The present study describes an improved method for measuring angiotensin III in arterial blood. This was accomplished by SE-sephadex column to separate angiotensin II from angiotensin III prior to radioimmunoassay. The arterial concentration of angiotensin III measured before and after 24 to 48 hours sodium depletion by acute cannulation of parotid gland was 12.4 ± 1.7 fmol/ml (SEM, n=7) and 49.8 ± 10.3 fmol/ml (SEM, n=7) respectively. The arterial concentration of Val4-angiotensin III obtained from continuous infusion of Val4-angiotensin III at rates of 24 and 48 nmol/h in sodium deficient sheep were 245 ± 32.5 fmol/ml (n=6) and 330 ± 11.4 fmol/ ml (n=7) respectively. The clearance rate of exogenous Val4-angiotensin III in sodium deficient sheep after correction for endogenous level was calculated to be 140 ± 13.6 L/h (SEM, n=13). This was in the same order as Ile5-angiotensin II and Ile4-angiotensin III reported earlier in sodium replete sheep. Prolonged intravenous infusion of Val4-angiotensin III at a rate of 48 nmol/h in sodium- deficient sheep suppressed plasma renin concentration to the same extent as equimolar infusions of angiotensin II. This suggests that angiotensin III may inhibit renin secretion by a similar mechanism to angiotensin II. 相似文献
103.
Christine Rasetti-Escargueil Arnaud Avril Siham Chahboun Rob Tierney Nicola Bak Sebastian Miethe Christelle Mazuet Michel R Popoff Philippe Thullier Michael Hust Thibaut Pelat Dorothea Sesardic 《MABS-AUSTIN》2015,7(6):1161-1177
Botulinum neurotoxins (BoNTs) are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agents by the Centers for Disease Control and Prevention. To date, 7 subtypes of BoNT/B were identified showing that subtypes B1 (16 strains) and B2 (32 strains) constitute the vast majority of BoNT/B strains. Neutralizing antibodies are required for the development of anti-botulism drugs to deal with the potential risk. In this study, macaques (Macaca fascicularis) were immunized with recombinant light chain (LC) or heavy chain (HC) of BoNT/B2, followed by the construction of 2 hyper-immune phage display libraries. The best single-chain variable fragments (scFvs) isolated from each library were selected according to their affinities and cross reactivity with BoNT/B1 toxin subtype. These scFvs against LC and HC were further analyzed by assessing the inhibition of in vitro endopeptidase activity of BoNT/B1 and B2 and neutralization of BoNT/B1 and B2 toxin-induced paralysis in the mouse ex vivo phrenic nerve assay. The antibodies B2–7 (against HC) and BLC3 (against LC) were produced as scFv-Fc, and, when tested individually, neutralized BoNT/B1 and BoNT/B2 in a mouse ex vivo phrenic nerve assay. Whereas only scFv-Fc BLC3 alone protected mice against BoNT/B2-induced paralysis in vivo, when B2–7 and BLC3 were combined they exhibited potent synergistic protection. The present study provided an opportunity to assess the extent of antibody-mediated neutralization of BoNT/B1 and BoNT/B2 subtypes in ex vivo and in vitro assays, and to confirm the benefit of the synergistic effect of antibodies targeting the 2 distinct functional domains of the toxin in vivo. Notably, the framework regions of the most promising antibodies (B2–7 and BLC3) are close to the human germline sequences, which suggest that they may be well tolerated in potential clinical development. 相似文献
104.
The rise and fall of arbuscular mycorrhizal fungal diversity during ecosystem retrogression 下载免费PDF全文
Manuela Krüger François P. Teste Etienne Laliberté Hans Lambers Megan Coghlan Graham Zemunik Michael Bunce 《Molecular ecology》2015,24(19):4912-4930
Ecosystem retrogression following long‐term pedogenesis is attributed to phosphorus (P) limitation of primary productivity. Arbuscular mycorrhizal fungi (AMF) enhance P acquisition for most terrestrial plants, but it has been suggested that this strategy becomes less effective in strongly weathered soils with extremely low P availability. Using next generation sequencing of the large subunit ribosomal RNA gene in roots and soil, we compared the composition and diversity of AMF communities in three contrasting stages of a retrogressive >2‐million‐year dune chronosequence in a global biodiversity hotspot. This chronosequence shows a ~60‐fold decline in total soil P concentration, with the oldest stage representing some of the most severely P‐impoverished soils found in any terrestrial ecosystem. The richness of AMF operational taxonomic units was low on young (1000's of years), moderately P‐rich soils, greatest on relatively old (~120 000 years) low‐P soils, and low again on the oldest (>2 000 000 years) soils that were lowest in P availability. A similar decline in AMF phylogenetic diversity on the oldest soils occurred, despite invariant host plant diversity and only small declines in host cover along the chronosequence. Differences in AMF community composition were greatest between the youngest and the two oldest soils, and this was best explained by differences in soil P concentrations. Our results point to a threshold in soil P availability during ecosystem regression below which AMF diversity declines, suggesting environmental filtering of AMF insufficiently adapted to extremely low P availability. 相似文献
105.
106.
107.
Forde BM Neville BA O'Donnell MM Riboulet-Bisson E Claesson MJ Coghlan A Ross RP O'Toole PW 《Microbial cell factories》2011,10(Z1):S13
Background
The genus Lactobacillus is characterized by an extraordinary degree of phenotypic and genotypic diversity, which recent genomic analyses have further highlighted. However, the choice of species for sequencing has been non-random and unequal in distribution, with only a single representative genome from the L. salivarius clade available to date. Furthermore, there is no data to facilitate a functional genomic analysis of motility in the lactobacilli, a trait that is restricted to the L. salivarius clade.Results
The 2.06 Mb genome of the bovine isolate Lactobacillus ruminis ATCC 27782 comprises a single circular chromosome, and has a G+C content of 44.4%. In silico analysis identified 1901 coding sequences, including genes for a pediocin-like bacteriocin, a single large exopolysaccharide-related cluster, two sortase enzymes, two CRISPR loci and numerous IS elements and pseudogenes. A cluster of genes related to a putative pilin was identified, and shown to be transcribed in vitro. A high quality draft assembly of the genome of a second L. ruminis strain, ATCC 25644 isolated from humans, suggested a slightly larger genome of 2.138 Mb, that exhibited a high degree of synteny with the ATCC 27782 genome. In contrast, comparative analysis of L. ruminis and L. salivarius identified a lack of long-range synteny between these closely related species. Comparison of the L. salivarius clade core proteins with those of nine other Lactobacillus species distributed across 4 major phylogenetic groups identified the set of shared proteins, and proteins unique to each group.Conclusions
The genome of L. ruminis provides a comparative tool for directing functional analyses of other members of the L. salivarius clade, and it increases understanding of the divergence of this distinct Lactobacillus lineage from other commensal lactobacilli. The genome sequence provides a definitive resource to facilitate investigation of the genetics, biochemistry and host interactions of these motile intestinal lactobacilli.108.
Julie Gonin Agnès Carlotti Céline Dietrich Anne Audebourg Brigitte Radenen-Bussière Anne Caignard Marie-Fran?oise Avril Marie-Cécile Vacher-Lavenu Frédérique Larousserie Odile Devergne 《PloS one》2013,8(10)
Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82) representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10. 相似文献
109.
In this paper, we present a new approach for velocity vector imaging and time-resolved measurements of strain rates in the wall of human arteries using MRI and we prove its feasibility on two examples: in vitro on a phantom and in vivo on the carotid artery of a human subject. Results point out the promising potential of this approach for investigating the mechanics of arterial tissues in vivo. 相似文献
110.
Coghlan DR Bremner JB Keller PA Pyne SG David DM Somphol K Baylis D Coates J Deadman J Rhodes DI Robertson AD 《Bioorganic & medicinal chemistry》2011,19(11):3549-3557
As part of a programme investigating antibacterial cyclic macrocycles containing a cationic amino acid with an internal aromatic hydrophobic scaffold, we previously reported a macrocycle anchored at the 3,3'-positions of a 1,1'-binaphthyl unit. This was prepared via key intermediates containing an internal allylglycine and an allyl-substituted binaphthyl unit for a subsequent ring-closing metathesis reaction. This paper presents some structure-activity relationship studies with additional macrocycles based on this lead compound against Staphylococcus aureus together with the antibacterial activity of two related acyclic compounds. 相似文献