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81.
82.
Ray C. Bartolo Natalie Harfoot Mike Gill Kristy Demmers Bernie McLeod A. Grant Butt 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2009,179(8):997-1010
The colon of the brushtail possum does not have an electrogenic secretory response. Given the functional significance of electrogenic
Cl− secretion in the intestine of eutherian mammals, we have investigated the secretory response in the small intestine of this
marsupial. In the Ussing chamber cAMP-dependent secretagogues stimulated a sustained increase in ileal short-circuit current
(Isc), whereas Ca2+-dependent secretagogues induced a transient increase. Both the responses were inhibited by mucosal addition of the anion
channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (100 μmol l−1), consistent with an anion secretory response. However, the responses were not inhibited by serosal bumetanide (10 μmol l−1) and were independent of bath Cl−, indicating that the stimulated ileal Isc does not involve electrogenic Cl− secretion driven by the NaK2Cl cotransporter, NKCC1. Consistent with this, there were low levels of NKCC1 expression in the
ileal epithelium. In particular, NKCC1 expression in the ileal crypt cells was comparable to that of the villous cells. This
differs from eutherian mammals where high levels of NKCC1 expression in the ileal crypt cells are associated with their role
in Cl− secretion. The cAMP- and Ca2+-dependent secretory responses were inhibited by the removal of HCO3
− suggesting that these responses were due to electrogenic HCO3
− secretion. We conclude that the ileum of the possum does not secrete Cl− due to low levels of NKCC1 expression. It does however appear to secrete HCO3
−. These results are further significant examples of differences in the transport function of the possum intestinal epithelium
compared with eutherian mammals. 相似文献
83.
c-Myc overexpression and endocrine resistance in breast cancer 总被引:5,自引:0,他引:5
84.
Adam W Clarke Lynn Poulton Hoi Yi Wai Stuart A Walker Shanti David Victor Teresa Domagala Dragana Mraovic Danyal Butt Nina Shewmaker Philip Jennings Anthony G Doyle 《MABS-AUSTIN》2010,2(5):539-549
While current therapeutic antibodies bind to IL-12 and IL-23 and inhibit their binding to IL-12Rβ1, we describe a novel antibody, termed 6F6, that binds to IL-12 and IL-23 and inhibits the interaction of IL-12 and IL-23 with their cognate signaling receptors IL-12Rβ2 and IL23R. This antibody does not affect the natural inhibition of the IL-12/23 pathway by the antagonists monomeric IL-12p40 and IL-12p80 respectively, which suggests that a dual antagonist system is possible. We have mapped the epitope of 6F6 to domain 3 of the p40 chain common to IL-12 and IL-23 and demonstrate that an antibody bound to this epitope is sufficient to inhibit engagement of the signaling receptors. Antibodies with this unique mechanism of inhibition are potent inhibitors of IL-12 induced IFNγ production and IL-23 induced IL-17 production in vitro, and in an in vivo model of psoriasis, treatment with a humanized variant of this antibody, h6F6, reduced the inflammatory response, resulting in decreased epidermal hyperplasia. We believe that this new class of IL-12/23 neutralising antibodies has the potential to provide improved potency and efficacy as anti-inflammatory agents, particularly in diseases characterized by an overproduction of IL-12.Key words: IL-12, IL-23, IL-12p40, IL-12 receptor, IL-12Rβ1, IL-12Rβ2, IL-23R, antibody, TH17, TH1 相似文献
85.
Buehler PW Butt OI D'Agnillo F 《Biochemical and biophysical research communications》2011,(3):412-417
Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO2) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO2, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity. 相似文献
86.
Field SJ Roldan MD Marritt SJ Butt JN Richardson DJ Watmough NJ 《Biochimica et biophysica acta》2011,1807(4):451-457
The active site of the bacterial nitric oxide reductase from Paracoccus denitrificans contains a dinuclear centre comprising heme b? and non heme iron (Fe(B)). These metal centres are shown to be at isopotential with midpoint reduction potentials of E(m) ≈ +80 mV. The midpoint reduction potentials of the other two metal centres in the enzyme, heme c and heme b, are greater than the dinuclear centre suggesting that they act as an electron receiving/storage module. Reduction of the low-spin heme b causes structural changes at the dinuclear centre which allow access to substrate molecules. In the presence of the substrate analogue, CO, the midpoint reduction potential of heme b? is raised to a region similar to that of heme c and heme b. This leads us to suggest that reduction of the electron transfer hemes leads to an opening of the active site which allows substrate to bind and in turn raises the reduction potential of the active site such that electrons are only delivered to the active site following substrate binding. 相似文献
87.
Chitosan is a promising biomaterial for biomedical applications and is currently applied as wound dressings. While chitosan
solutions demonstrate strong bactericidal activity against a range of medically important bacteria, the study here reports
a loss of this beneficial property in thin films cast from the same solutions. Chitosan films (20 μm) showed no inhibitory
effects against Escherichia coli, Staphylococcus aureus or S. epidermidis species. In contrast, solutions used to prepare the films showed almost complete inhibition (~98 ± 2%) when tested on bacterial
lawns and in liquid cultures. Increased acidity of the chitosan solutions (pH 5) was shown to promote the bactericidal effects
of this biopolymer. The concept that devices fabricated from chitosan have an inherent antimicrobial activity is suggested
as an important misconception. 相似文献
88.
Saima Chaudhry Muhammad Idrees Mateen Izhar Arshad Kamal Butt Ayyaz Ali Khan 《Current microbiology》2011,62(1):78-83
Polymerase Chain reaction (PCR) assay is considered superior to other methods for detection of Helicobacter pylori (H. pylori) in oral cavity; however, it also has limitations when sample under study is microbial rich dental plaque. The type of gene
targeted and number of primers used for bacterial detection in dental plaque samples can have a significant effect on the
results obtained as there are a number of closely related bacterial species residing in plaque biofilm. Also due to high recombination
rate of H. pylori some of the genes might be down regulated or absent. The present study was conducted to determine the frequency of H. pylori colonization of dental plaque by simultaneously amplifying two genes of the bacterium. One hundred dental plaque specimens
were collected from dyspeptic patients before their upper gastrointestinal endoscopy and presence of H. pylori was determined through PCR assay using primers targeting two different genes of the bacterium. Eighty-nine of the 100 samples
were included in final analysis. With simultaneous amplification of two bacterial genes 51.6% of the dental plaque samples
were positive for H. pylori while this prevalence increased to 73% when only one gene amplification was used for bacterial identification. Detection
of H. pylori in dental plaque samples is more reliable when two genes of the bacterium are simultaneously amplified as compared to one
gene amplification only. 相似文献
89.
Arnold LH Butt LE Prior SH Read CM Fields GB Pickford AR 《The Journal of biological chemistry》2011,286(52):45073-45082
Matrix metalloproteinase-1 (MMP-1) is an instigator of collagenolysis, the catabolism of triple helical collagen. Previous studies have implicated its hemopexin (HPX) domain in binding and possibly destabilizing the collagen substrate in preparation for hydrolysis of the polypeptide backbone by the catalytic (CAT) domain. Here, we use biophysical methods to study the complex formed between the MMP-1 HPX domain and a synthetic triple helical peptide (THP) that encompasses the MMP-1 cleavage site of the collagen α1(I) chain. The two components interact with 1:1 stoichiometry and micromolar affinity via a binding site within blades 1 and 2 of the four-bladed HPX domain propeller. Subsequent site-directed mutagenesis and assay implicates blade 1 residues Phe(301), Val(319), and Asp(338) in collagen binding. Intriguingly, Phe(301) is partially masked by the CAT domain in the crystal structure of full-length MMP-1 implying that transient separation of the domains is important in collagen recognition. However, mutation of this residue in the intact enzyme disrupts the CAT-HPX interface resulting in a drastic decrease in binding activity. Thus, a balanced equilibrium between these compact and dislocated states may be an essential feature of MMP-1 collagenase activity. 相似文献
90.
Leif Brottem Matthew D. Turner Bilal Butt Aditya Singh 《Human ecology: an interdisciplinary journal》2014,42(3):351-365
This paper focuses on a conundrum that has dominated the literature on pastoral mobility and institutions in dryland regions of the world, where livestock production is the main livelihood system. High spatiotemporal variability of rainfall and forage resources are seen to require flexible rules and porous social boundaries to facilitate pastoral mobility—characteristics that run counter to conventional views of the requirements for effective common property institutions. We seek to explore this paradox by investigating the spatiotemporal variability of forage availability (using satellite derived vegetation indices as a proxy for green forage) in four transhumance zones (“transhumance sheds”) in Mali, West Africa. For each transhumance shed, three characteristics with important institutional implications are evaluated over an eleven-year period between 2000 and 2010: the inter-annual variability of forage phenology, seasonal changes in connectivity of green forage patches, and the degree to which key forage locations exist in the form of consistently early green-up and/or late senescence. Periods of vegetation green-up and senescence, which determine the timing of transhumant livestock movements, are found to be sufficiently regular from year to year to be governed by conventional institutions. Seasonal changes in the north-south connectivity of green patches are sufficiently rapid for customary systems of sharing of pasture information to be effective (rather than more technologically sophisticated systems of pasture information). Moreover, transhumance sheds contain key pastoral forage sites, which because of their consistently early greening or late senescence, are strong candidates for territorial protection from alternative land uses such as agriculture. These findings support local herders’ views of transhumance as composed of regular patterns of herd movements along prescribed corridors between key pastoral sites. The seasonal regularity of key pastoral resources has been obscured by an overemphasis on environmental unpredictability that characterizes dryland systems at certain spatial and temporal scales. This paper suggests that policies directed at improving pastoral resource governance must focus instead on securing pastoralists’ access rights to movement corridors, specific pastures and water points. 相似文献