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61.
MscL, a mechanosensitive channel found in many bacteria, protects cells from hypotonic shock by reducing intracellular pressure through release of cytoplasmic osmolytes. First isolated from Escherichia coli, this protein has served as a model for how a protein senses and responds to membrane tension. Recently the structure of a functionally uncharacterized MscL homologue from Mycobacterium tuberculosis was solved by x-ray diffraction to a resolution of 3.5 A. Here we demonstrate that the protein forms a functional MscL-like mechanosensitive channel in E. coli membranes and azolectin proteoliposomes. Furthermore, we show that M. tuberculosis MscL crystals, when re-solubilized and reconstituted, yield wild-type channel currents in patch clamp, demonstrating that the protein does not irreversibly change conformation upon crystallization. Finally, we apply functional clues acquired from the E. coli MscL to the M. tuberculosis channel and show a mechanistic correlation between these channels. However, the inability of the M. tuberculosis channel to gate at physiological membrane tensions, demonstrated by in vivo E. coli expression and in vitro reconstitution, suggests that the membrane environment or other additional factors influence the gating of this channel. 相似文献
62.
63.
Because the H2O2 and O2
− generated during a pathogen-triggered oxidative burst could either protect or destroy a besieged plant cell, their synthesis
might be expected to be tightly regulated. We have examined the nature of this regulation as it is communicated between homologous
and heterologous oxidative-burst pathways, using both chemical (oligogalacturonic acid, harpin, fensulfothion) and mechanical
(osmotic stress) stimuli to induce the burst. We report here that the above three chemical elicitors attenuate a subsequent
oxidative burst induced in cultured soybean (Glycine max L.) cells by either the same (homologous desensitization) or a different chemical elicitor (heterologous desensitization).
Further, when the magnitude of the initial oxidative burst is maximal, the cells remain refractory to subsequent elicitation
for at least 10 min and then revive their sensitivities to re-stimulation with a half-time of >20 min. Mechanical stimulation
of the oxidative burst appears to be regulated by a different set of constraints. Although initiation of a mechanically induced
burst leads to attenuation of a subsequent mechanically induced burst, the same mechanical stimulus is peculiarly unable to
reduce a subsequent chemically induced burst. The converse is also true, suggesting that heterologous desensitization of the
oxidative burst does not extend to mixed chemical and mechanical/osmotic stimuli. However, communication between these disparate
forms of elicitation is still demonstrated to occur, since low-level chemical stimuli strongly synergize concurrent low-level
osmotic stimuli and vice versa. Furthermore, the pattern of synergy changes dramatically if one stimulus is administered immediately
prior to the other. Taken together, these data demonstrate that significant cross-talk occurs among the different signaling
pathways of the oxidative burst and that the overall process is tightly regulated.
Received: 10 January 2000 / Accepted: 22 February 2000 相似文献
64.
65.
Genomic Resources Development Consortium Mariella Baratti Federica Cattonaro Tiziana Di Lorenzo Diana Maria Paola Galassi Valentina Iannilli Alessio Iannucci Just Jensen Peter Foged Larsen Rasmus O. Nielsen Cino Pertoldi Dragos Postolache Jose Martin Pujolar Ettore Randi Aritz Ruiz‐Gonzalez Janne Pia Thirstrup Giovanni Giuseppe Vendramin Andrzej Zalewski 《Molecular ecology resources》2015,15(2):458-459
66.
Nang Thu Thu Kyaw Anthony D. Harries Palanivel Chinnakali Annick Antierens Kyi Pyar Soe Mike Woodman Mrinalini Das Sharmila Shetty Moe Khine Lwin Zuu Pyae Sone Htwe Marcelo Fernandez 《PloS one》2015,10(8)
Background
Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction.Methods
We used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50ml/min/1.73m2. We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors.Results
There were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30–50ml/min/1.73m2 and were maintained on TDF–based ART, but 5 were changed to another regimen: 4 because of CrCl <30ml/min/1.73m2. Risk factors for renal dysfunction included age ≥45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200cells/mm3. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30–49 ml/min/1.73m2 in five patients while the remainder regained normal renal function.Conclusions
In a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit. 相似文献67.
David Pimentel Michele Whitecraft Zachary R. Scott Leixin Zhao Patricia Satkiewicz Timothy J. Scott Jennifer Phillips Daniel Szimak Gurpreet Singh Daniela O. Gonzalez Tun Lin Moe 《Human ecology: an interdisciplinary journal》2010,38(5):599-611
Nearly 60% of the world’s human population is malnourished and the numbers are growing. Shortages of basic foods related to decreases in per capita cropland, water, and fossil energy resources contribute to spreading malnutrition and other diseases. The suggestion is that in the future only a smaller number of people will have access to adequate nourishment. In about 100 years, when it is reported that the planet will run out of fossil energy, we suggest that a world population of about two billion might be sustainable if it relies on renewable energy technologies and also reduces per capita use of the earth’s natural resources. 相似文献
68.
V. Gervasi P. Ciucci F. Davoli J. Boulanger L. Boitani E. Randi 《Conservation Genetics》2010,11(6):2299-2310
It is often difficult to determine optimal sampling design for non-invasive genetic sampling, especially when dealing with
rare or elusive species depleted of genetic diversity. To address this problem, we ran a hair-snag pilot study on the remnant
Apennine brown bear population. We used occupancy models to estimate the performance of an improved field protocol, a meta-analysis
approach to indirectly model capture probability, and simulations to evaluate the effect of genotyping errors on the accuracy
of capture-recapture population estimates. In spring 2007 we collected 70 bear hair samples in 15 5 × 5 km cells, using 5
10-day trapping sessions. Bear detectability was higher in 2007 than in a previous attempt on the same population in 2004,
reflecting improved field protocols and sampling design. However, individual capture probability was 0.136 (95% CI = 0.120–0.152),
still below the minimum requirements of capture-mark-recapture closed population models. We genotyped hair samples (n = 63) at 9 microsatellite loci, obtaining 94% Polymerase Chain Reaction success, and 13 bear genotypes. Estimated PIDsib was 0.00594, and per-genotype error rate was 0.13, corresponding to a 99% probability of correct individual identification.
Simulation studies showed that the effect of non-corrected or filtered genetic errors on the accuracy of population estimates
was negligible only when individual capture probability was >0.2. Our results underline how the interaction among field protocols,
sampling strategies and genotyping errors may affect the accuracy of DNA-based estimates of small and genetically depleted
populations, and warned us about the feasibility of a survey using only traditional hair-snag sampling. In this and similar
cases, indications from pilot studies can provide cost-effective means to evaluate the efficiency of designed sampling and
modelling procedures. 相似文献
69.
Barnickel B Bayliffe F Diestel R Kempf K Laschat S Pachali S Sasse F Schlenk A Schobert R 《化学与生物多样性》2010,7(12):2830-2845
Fragments and synthetic precursors prepared en route to the macrocyclic 3-acyltetramic acids (=3-acyl-1,5-dihydro-4-hydroxy-2H-pyrrol-2-ones) aburatubolactam and macrocidin A, as well as other analogs with variance in the ring heteroatom (N, O, S), and the residues at N(1), C(3), and C(5) were tested for cytotoxic and antimicrobial effects. Anticancer activity against various tumor cell lines in vitro did not necessarily require an intact pyrrolidin-2,4-dione ring. An acyclic β-hydroxy-octatrienoyl amide precursor to aburatubolactam also exhibited distinct activity with an IC?? (120?h) value of <2.5?μM. The length of 3-oligoenoyl residues had little influence on the anticancer activity, but 3-alka-oligoenoyl tetramic acids were far more efficacious than their 3-(4-methoxycinnamoyl) congeners. N-H-3-acyltetramic acids were generally more active than their N-Me or N-Boc analogs, unless further polar groups necessitated an increased lipophilicity for sufficient uptake. Tetronic and thiotetronic acids were far less antiproliferative in cancer cells when compared with identically substituted tetramic acids. 相似文献
70.
Phospholipid hydrolysis caused by Clostridium perfringens α-toxin facilitates the targeting of perfringolysin O to membrane bilayers 总被引:1,自引:0,他引:1
Clostridium perfringens causes gas gangrene and gastrointestinal disease in humans. These pathologies are mediated by potent extracellular protein toxins, particularly α-toxin and perfringolysin O (PFO). While α-toxin hydrolyzes phosphatidylcholine and sphingomyelin, PFO forms large transmembrane pores on cholesterol-containing membranes. It has been suggested that the ability of PFO to perforate the membrane of target cells is dictated by how much free cholesterol molecules are present. Given that C. perfringens α-toxin cleaves the phosphocholine headgroup of phosphatidylcholine, we reasoned that α-toxin may increase the number of free cholesterol molecules in the membrane. Our present studies reveal that α-toxin action on membrane bilayers facilitates the PFO?cholesterol interaction as evidenced by a reduction in the amount of cholesterol required in the membrane for PFO binding and pore formation. These studies suggest a mechanism for the concerted action of α-toxin and PFO during C. perfringens pathogenesis. 相似文献