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71.
A survey of ethics committees in district health authorities was carried out to find out the size and make up of committees and what information and guidance they offered to scientists who apply to do research. A sample (n = 28) of committees in England (n = 190), half from teaching districts and half from non-teaching districts, was contacted by post requesting this information. A high degree of diversity was found, not only in the methods that committees used but also in the ethical criteria each considered to be pertinent for research. It was also shown that published guidelines have made little impact. It is suggested that issuing more guidelines will be of limited use. Rather, the following are needed: information about why guidelines have been widely ignored, better communication between committees, some form of education for committee members, and a formal register of committees compiled. 相似文献
72.
Timothy R. Holzer Angie D. Fulford Drew M. Nedderman Tara S. Umberger Rebecca R. Hozak Adarsh Joshi Symantha A. Melemed Laura E. Benjamin Gregory D. Plowman Andrew E. Schade Bradley L. Ackermann Robert J. Konrad Aejaz Nasir 《PloS one》2013,8(11)
A robust immunohistochemical (IHC) assay for VEGFR2 was developed to investigate its utility for patient tailoring in clinical trials. The sensitivity, specificity, and selectivity of the IHC assay were established by siRNA knockdown, immunoblotting, mass spectrometry, and pre-absorption experiments. Characterization of the assay included screening a panel of multiple human cancer tissues and an independent cohort of non-small cell lung carcinoma (NSCLC, n = 118) characterized by TTF-1, p63, CK5/6, and CK7 IHC. VEGFR2 immunoreactivity was interpreted qualitatively (VEGFR2 positive/negative) in blood vessels and by semi-quantitative evaluation using H-scores in tumor cells (0–300). Associations were determined among combinations of VEGFR2 expression in blood vessels and tumor cells, and clinico-pathologic characteristics (age, sex, race, histologic subtype, disease stage) and overall survival using Kaplan-Meier analyses and appropriate statistical models. VEGFR2 expression both in blood vessels and in tumor cells in carcinomas of the lung, cervix, larynx, breast, and others was demonstrated. In the validation cohort, 99/118 (83.9%) NSCLC tissues expressed VEGFR2 in the blood vessels and 46/118 (39.0%) showed high tumor cell positivity (H-score ≥10). Vascular and tumor cell expression were inversely correlated (p = 0.0175). High tumor cell expression of VEGFR2 was associated with a 3.7-fold reduction in median overall survival in lung squamous-cell carcinoma (SCC, n = 25, p = 0.0134). The inverse correlation between vascular and tumor cell expression of VEGFR2 and the adverse prognosis associated with high VEGFR2 expression in immunohistochemically characterized pulmonary SCC are new findings with potential therapeutic implications. The robustness of this novel IHC assay will support further evaluation of its utility for patient tailoring in clinical trials of antiangiogenic agents. 相似文献
73.
In seasonal environments with limited time and energy resources, double‐brooded birds face trade‐offs in the timing of their two reproductive attempts and in the effort allocated to the first and the second broods. In the Barn Swallow Hirundo rustica a long care period for the first brood enhances the survival of first‐brood chicks, but also delays the start of the second brood, which in turn reduces the survival prospects of second‐brood chicks. Probably as a response to this trade‐off, double‐brooded Barn Swallows reduce the period of post‐fledging care for first‐brood fledglings. By radiotracking whole families, we investigated the determinants of this behaviour and its consequences for the survival of the first‐brood fledglings. The end of the females’ investment in post‐fledging care of the first brood was related to the beginning of egg synthesis for the second clutch. With the start of egg synthesis, females significantly reduced provisioning rates to the first‐brood fledglings to less than one‐fifth of the previous rates, while the proportion of time they spent foraging remained high. Assuming that the females’ foraging success was constant, we conclude that their energy income was allocated to egg production rather than fledgling provision. Males did not compensate for the females’ reduced feeding rates. Thus the start of egg production for the second clutch had a marked effect on the quantity of food received by first‐brood fledglings. In parallel with the changes in parental behaviour and provisioning rates, we observed a marked drop in the daily survival rate of first‐brood chicks. These results support the hypothesis that females face a strong trade‐off in the allocation of energy to subsequent broods. Energy allocation to a second clutch involves a cost in terms of reduced provisioning, and as a result the survival of first‐brood chicks is compromised. This is probably outweighed by the improved success of an early second brood. 相似文献
74.
75.
Susana Scott Aderonke Odutola Grant Mackenzie Tony Fulford Muhammed O. Afolabi Yamundow Lowe Jallow Momodou Jasseh David Jeffries Bai Lamin Dondeh Stephen R. C. Howie Umberto D'Alessandro 《PloS one》2014,9(9)
Objective
To evaluate the coverage and timeliness of the Expanded Programme on Immunisation (EPI) in The Gambia.Methods
Vaccination data were obtained between January 2005 and December 2012 from the Farafenni Health and Demographic Surveillance System (FHDSS), the Basse Health and Demographic Surveillance System (BHDSS), the Kiang West Demographic surveillance system (KWDSS), a cluster survey in the more urban Western Health Region (WR) and a cross sectional study in four clinics in the semi-urban Greater Banjul area of WR. Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and to assess timeliness to vaccination.Findings
BCG vaccine uptake was over 95% in all regions. Coverage of DPT1 ranged from 93.2% in BHDSS to 99.8% in the WR. Coverage decreased with increasing number of DPT doses; DPT3 coverage ranged from 81.7% in BHDSS to 99.0% in WR. Measles vaccination coverage ranged from 83.3% in BHDSS to 97.0% in WR. DPT4 booster coverage was low and ranged from 43.9% in the WR to 82.8% in KWDSS. Across all regions, delaying on previous vaccinations increased the likelihood of being delayed for the subsequent vaccination.Conclusions
The Gambia health system achieves high vaccine coverage in the first year of life. However, there continues to be a delay to vaccination which may impact on the introduction of new vaccines. Examples of effectively functioning EPI programmes such as The Gambia one may well be important models for other low income countries struggling to achieve high routine vaccination coverage. 相似文献76.
77.
The signature DNA lesion induced by ionizing radiation is clustered DNA damage. Gamma radiation-induced clustered DNA damage containing base lesions was investigated in plasmid DNA under cell mimetic conditions and in two cell lines, V79-4 (hamster) and HF19 (human), using bacterial endonucleases Nth (endonuclease III) and Fpg (formamidopyrimidine DNA glycosylase). Following irradiation with 60Co γ-rays, induction of double-strand breaks (DSB) and clustered DNA damage, revealed as DSB by the proteins, was determined in plasmid using the plasmid-nicking assay and in cells by either conventional pulsed field gel electrophoresis or a hybridization assay, in which a 3 Mb restriction fragment of the X chromosome is used as a radioactive labeled probe. Enzyme concentrations (30–60 ng/µg DNA) were optimized to minimize visualization of background levels of endogenous DNA damage and DSB produced by non-specific cutting by Fpg and Nth in cellular DNA. 60Co γ- radiation produces a 1.8-fold increase in the yields of both types of enzyme sensitive sites, visualized as DSB compared with that of prompt DSB in plasmid DNA. In mammalian cells, the increase in yields of clustered DNA damage containing either Fpg or Nth sensitive sites compared with that of prompt DSB is 1.4–2.0- and 1.8-fold, respectively. Therefore, clustered DNA damage is induced in cells by sparsely ionizing radiation and their yield is significantly greater than that of prompt DSB. 相似文献
78.
Cytolytic activity of Naegleria fowleri cell-free extract 总被引:4,自引:0,他引:4
The cytotoxic activity of a cell-free extract of Naegleria fowleri amebae on B103 rat nerve cells in culture was investigated. The cell-free extract was prepared by subjecting lysed amebae to centrifugation at 100,000 g for 1 h, precipitation of the supernatant fluid with 30-60% saturated ammonium sulfate, and desalting by group exclusion chromatography utilizing Sephadex G-25. The supernatant fluid recovered from this procedure was termed the soluble fraction. The Naegleria cytotoxic activity present in the soluble fraction was assayed by 51Cr released from labeled B103 cells. The Naegleria soluble fraction, when added to nerve cells, elicited blebs on the B103 target cell surface within 5 min after exposure to the fraction. Later, holes were observed in the B103 cell plasma membrane. These alterations were never observed on untreated B103 cells. Phospholipase A, phospholipase C, and protease activities were associated with the desalted ammonium sulfate-precipitable cytotoxic activity of N. fowleri cell-free lysate. The cytotoxic activity was impaired by ethylenediamine-tetraacetate (EDTA), phospholipase A inhibitor (Rosenthal's reagent), heating at 50 degrees C for 15 min, or incubation at pH 10 for 60 min. Repeated freeze-thawing and inhibitors of proteolytic enzymes had no effect on the cytotoxic activity. Small amounts of ethanol (5% v/v) enhanced cytotoxic activity of the fraction. Phospholipases A and C, as well as other as yet unidentified cytolytic factors may be responsible for producing 51Cr release from target cells by the soluble fraction of N. fowleri extracts. 相似文献
79.
Howe GT; Bucciaglia PA; Hackett WP; Furnier GR; Cordonnier-Pratt MM; Gardner G 《Molecular biology and evolution》1998,15(2):160-175
The phytochrome photoreceptors play important roles in the photoperiodic
control of vegetative bud set, growth cessation, dormancy induction, and
cold-hardiness in trees. Interestingly, ecotypic differences in
photoperiodic responses are observed in many temperate- zone tree species.
Northern and southern ecotypes of black cottonwood (Populus trichocarpa
Torr. & Gray), for example, exhibit marked differences in the timing of
short-day-induced bud set and growth cessation, and these responses are
controlled by phytochrome. Therefore, as a first step toward determining
the molecular genetic basis of photoperiodic ecotypes in trees, we
characterized the phytochrome gene (PHY) family in black cottonwood. We
recovered fragments of one PHYA and two PHYB using PCR-based cloning and by
screening a genomic library. Results from Southern analyses confirmed that
black cottonwood has one PHYA locus and two PHYB loci, which we arbitrarily
designated PHYB1 and PHYB2. Phylogenetic analyses which included PHY from
black cottonwood, Arabidopsis thaliana and tomato (Solanum lycopersicum)
suggest that the PHYB/D duplications in these species occurred
independently. When Southern blots were probed with PHYC, PHYE, and PHYE
heterologous probes, the strongest bands that we detected were those of
black cottonwood PHYA and/or PHYB. These results suggest that black
cottonwood lacks members of the PHYC/F and PHYE subfamilies. Although black
cottonwood could contain additional PHY that are distantly related to known
angiosperm PHY, our results imply that the PHY family of black cottonwood
is less complex than that of other well-characterized dicot species such as
Arabidopsis and tomato. Based on Southern analyses of five black cottonwood
genotypes representing three photoperiodic ecotypes, substantial
polymorphism was detected for at least one of the PHYB loci but not for the
PHYA locus. The novel character of the PHY family in black cottonwood, as
well as the differences in polymorphism we observed between the PHYA and
PHYB subfamilies, indicates that a number of fundamental macro- and
microevolutionary questions remain to be answered about the PHY family in
dicots.
相似文献
80.
C.L. Bashford G.M. Alder L.G. Fulford Y.E. Korchev E. Kovacs A. MacKinnon C. Pederzolli C.A. Pasternak 《The Journal of membrane biology》1996,150(1):37-45
Nonelectrolytes such as polyethylene glycols (PEG) and dextrans (i) promote the association of S. aureus α-toxin with liposomes (shown by Coomassie staining) and (ii) enhance the rate and extent of calcein leakage from calcein-loaded
liposomes; such leakage is inhibited by H+, Zn2+ and Ca2+ to the same extent as that of nonPEG-treated liposomes. Incubation of liposomes treated with α-toxin in the presence of PEG
with the hydrophobic photo-affinity probe 3-(trifluoromethyl)-3-m-[125I]iodophenyl)diazirine(125I-TID) labels monomeric and—predominantly—hexameric forms of liposome-associated α-toxin; in the absence of PEG little labeling
is apparent. At high concentrations of H+ and Zn2+ but not of Ca2+—all of which inhibit calcein leakage—the distribution of label between hexamer and monomer is perturbed in favor of the latter.
In α-toxin-treated planar lipid bilayers from which excess toxin has been washed away, PEGs and dextrans strongly promote
the appearance of ion-conducting pores. The properties of such pores are similar in most regards to pores induced in the absence
of nonelectrolytes; they differ only in being more sensitive to ``closure' by voltage (as are pores induced in cells). In
both systems, the stimulation by nonelectrolytes increases with concentration and with molecular mass up to a maximum around
2,000 Da. We conclude (i) that most of the α toxin that becomes associated with liposome or planar lipid bilayers does not
form active pores and (ii) that the properties of α-toxin-induced pores in lipid bilayers can be modulated to resemble those
in cells.
Received: 2 October 1995/Revised: 3 November 1995 相似文献