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21.
Anti-CD20 monoclonal antibodies have been successfully employed in the clinical treatment of non-Hodgkin's lymphomas in both
unmodified and radiolabeled forms. Previous publications have demonstrated that the antitumor effects of unmodified anti-CD20
mAb are mediated by several mechanisms including antibody-dependent cellular cytotoxicity, complement-mediated cell lysis,
and induction of apoptosis by CD20 cross-linking. In this report, we demonstrate induction of apoptosis by three anti-CD20
monoclonal antibodies [1F5, anti-B1, and C2B8 (Rituximab)]. The magnitude of apoptosis induction was greater with the chimeric
Rituximab antibody than with the murine 1F5 and anti-B1 antibodies. Apoptosis could be enhanced with any of the antibodies
by cross-linking with secondary antibodies (or Fc-receptor-bearing accessory cells). The signaling events involved in anti-CD20-induced
apoptosis were investigated, including activation of protein tyrosine kinases, increases in intracellular Ca2+ concentrations, caspase activation, and cleavage of caspase substrates. Our results indicate that anti-CD20-induced apoptosis
can be attenuated by PP1, an inhibitor of protein tyrosine kinases Lck and Fyn, chelators of extracellular or intracellular
Ca2+, and inhibitors of caspases, suggesting that anti-CD20-induced apoptosis may involve modulation of these signaling molecules.
We also demonstrated that varying the expression of Bcl-2 did not affect the magnitude of anti-B1-induced apoptosis, possibly
because of the sequestering effects of other Bcl-2 family members, such as Bad. These studies identify several of the signal-transduction
events involved in the apoptosis of malignant B cells that transpire following ligation of CD20 by anti-CD20 antibodies in
the presence of Fc-receptor-expressing cells or secondary goat anti-(mouse Ig) antibodies and which may contribute to the
tumor regressions observed in mouse models and clinical trials.
Received: 27 May 1999 / Accepted: 1 October 1999 相似文献
22.
J. M. Hibberd R. A. Bungard M. C. Press W. D. Jeschke J. D. Scholes W. P. Quick 《Planta》1998,205(4):506-513
Cells capable of photosynthesis in the parasitic angiosperm Cuscuta reflexa Roxb. (dodder) are highly localized. Immunolocalization of ribulose-1,5 bisphosphate carboxylase-oxygenase (Rubisco) and
autofluorescence of chlorophyll in transverse sections of stems showed that they were largely restricted to a band of cells
adjacent to the vascular bundles, consequently, the concentrations of Rubisco and chlorophyll were low per unit area or fresh
weight. When 14CO2 was supplied to stem segments of C. reflexa it preferentially accumulated in these cells adjacent to the vasculature. Although the conductance for CO2 movement to the cells containing chlorophyll and Rubisco was very low, both the light reactions and dark reactions of photosynthesis
appeared to be functional. De-epoxidation of the xanthophyll-cycle pigments after exposure to high light, and the chlorophyll
fluorescence parameters, photochemical quenching (qP), non-photochemical quenching (NPQ) and the quantum efficiency of photosystem
II (φPSII) responded normally to changes in photon flux density, indicating functional light-driven electron transport. The
response of CO2 exchange to photon flux density followed a typical hyperbolic curve, and positive rates of CO2 fixation occurred when external CO2 was increased to 5%. We propose that CO2 for carbon assimilation is derived from internally respired CO2 and that this layer of photosynthetic cells makes a positive contribution to the carbon budget of C. reflexa.
Received: 23 October 1997 / Accepted: 16 December 1997 相似文献
23.
24.
Pasquier CM; Promponas VI; Varvayannis NJ; Hamodrakas SJ 《Bioinformatics (Oxford, England)》1998,14(8):749-750
Summary : FT is a tool written in C++, which implements the Fourier
analysis method to locate periodicities in aminoacid or DNA sequences. It
is provided for free public use on a WWW server with a Java interface.
Availability : The server address is http://o2.db. uoa.gr/FT Contact :
shamodr@atlas.uoa.gr
相似文献
25.
Pauline Rival Maximilian O. Press Jacob Bale Tanya Grancharova Soledad F. Undurraga Christine Queitsch 《Genetics》2014,198(2):747-754
It is widely appreciated that short tandem repeat (STR) variation underlies substantial phenotypic variation in organisms. Some propose that the high mutation rates of STRs in functional genomic regions facilitate evolutionary adaptation. Despite their high mutation rate, some STRs show little to no variation in populations. One such STR occurs in the Arabidopsis thaliana gene PFT1 (MED25), where it encodes an interrupted polyglutamine tract. Although the PFT1 STR is large (∼270 bp), and thus expected to be extremely variable, it shows only minuscule variation across A. thaliana strains. We hypothesized that the PFT1 STR is under selective constraint, due to previously undescribed roles in PFT1 function. We investigated this hypothesis using plants expressing transgenic PFT1 constructs with either an endogenous STR or synthetic STRs of varying length. Transgenic plants carrying the endogenous PFT1 STR generally performed best in complementing a pft1 null mutant across adult PFT1-dependent traits. In stark contrast, transgenic plants carrying a PFT1 transgene lacking the STR phenocopied a pft1 loss-of-function mutant for flowering time phenotypes and were generally hypomorphic for other traits, establishing the functional importance of this domain. Transgenic plants carrying various synthetic constructs occupied the phenotypic space between wild-type and pft1 loss-of-function mutants. By varying PFT1 STR length, we discovered that PFT1 can act as either an activator or repressor of flowering in a photoperiod-dependent manner. We conclude that the PFT1 STR is constrained to its approximate wild-type length by its various functional requirements. Our study implies that there is strong selection on STRs not only to generate allelic diversity, but also to maintain certain lengths pursuant to optimal molecular function. 相似文献
26.
Campan M Moffitt M Houshdaran S Shen H Widschwendter M Daxenbichler G Long T Marth C Laird-Offringa IA Press MF Dubeau L Siegmund KD Wu AH Groshen S Chandavarkar U Roman LD Berchuck A Pearce CL Laird PW 《PloS one》2011,6(12):e28141
Background
The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer.Methodology/Principal Findings
We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels.We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients.Conclusions/Significance
We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. 相似文献27.
To evaluate the dependence of the differentiation of the follicle-associated epithelium (FAE) on the presence of follicular B-cells, the FAE of ileal Peyers patch follicles was examined in B-cell-depleted fetal lambs. The FAE of these rudimentary follicles, which are devoid of lymphocytes, showed normal differentiation, including carbonic anhydrase reactivity and ultrastructural characteristics of transcytosis, extensive interdigitation of the lateral plasma membrane and the shedding of membrane-bounded particles, approximately 50 nm in size, resembling exosomes. These 50-nm membrane-bounded particles were abundant in the extracellular space of the epithelium and the dome but no particles were found in the rudimentary follicles. This study confirms that the rudimentary follicles consist of clusters of follicular dendritic cells. Our findings suggest that the differentiation of FAE of ileal Peyers patch and the production of the 50-nm particles constitute features that appear to be independent of B-cells. This study was supported in part by grants from the Norwegian Research Council 相似文献
28.
The root hemiparasitic weed Striga hermonthica is a serious constraint to grain production of economically important cereals in sub-Saharan Africa. Breeding for parasite resistance in cereals is widely recognized as the most sustainable form of long-term control; however, advances have been limited owing to a lack of cereal germplasm demonstrating postattachment resistance to Striga. Here, we identify a cultivar of rice (Nipponbare) that exhibits strong postattachment resistance to S. hermonthica; the parasite penetrates the host root cortex but does not form parasite-host xylem-xylem connections. In order to identify the genomic regions contributing to this resistance, a mapping population of backcross inbred lines between the resistant (Nipponbare) and susceptible (Kasalath) parents were evaluated for resistance to S. hermonthica. Composite interval mapping located seven putative quantitative trait loci (QTL) explaining 31% of the overall phenotypic variance; a second, independent, screen confirmed four of these QTL. Relative to the parental lines, allelic substitutions at these QTL altered the phenotype by at least 0.5 of a phenotypic standard deviation. Thus, they should be regarded as major genes and are likely to be useful in breeding programmes to enhance host resistance. 相似文献
29.
Cornelissen JH Quested HM van Logtestijn RS Pérez-Harguindeguy N Gwynn-Jones D Díaz S Callaghan TV Press MC Aerts R 《Oecologia》2006,147(2):315-326
Plant traits have become popular as predictors of interspecific variation in important ecosystem properties and processes.
Here we introduce foliar pH as a possible new plant trait, and tested whether (1) green leaf pH or leaf litter pH correlates
with biochemical and structural foliar traits that are linked to biogeochemical cycling; (2) there is consistent variation
in green leaf pH or leaf litter pH among plant types as defined by nutrient uptake mode and higher taxonomy; (3) green leaf
pH can predict a significant proportion of variation in leaf digestibility among plant species and types; (4) leaf litter
pH can predict a significant proportion of variation in leaf litter decomposability among plant species and types. We found
some evidence in support of all four hypotheses for a wide range of species in a subarctic flora, although cryptogams (fern
allies and a moss) tended to weaken the patterns by showing relatively poor leaf digestibility or litter decomposability at
a given pH. Among seed plant species, green leaf pH itself explained only up to a third of the interspecific variation in
leaf digestibility and leaf litter up to a quarter of the interspecific variation in leaf litter decomposability. However,
foliar pH substantially improved the power of foliar lignin and/or cellulose concentrations as predictors of these processes
when added to regression models as a second variable. When species were aggregated into plant types as defined by higher taxonomy
and nutrient uptake mode, green-specific leaf area was a more powerful predictor of digestibility or decomposability than
any of the biochemical traits including pH. The usefulness of foliar pH as a new predictive trait, whether or not in combination
with other traits, remains to be tested across more plant species, types and biomes, and also in relation to other plant or
ecosystem traits and processes. 相似文献
30.
The present study reports the quantitative analysis of the spatio-temporal development of nodavirus infection and corresponding immune response in juvenile Atlantic halibut (Hippoglossus hippoglossus) challenged by intramuscular injection of nodavirus. Novel quantitative real-time RT-PCR protocols were applied to evaluate the absolute copy numbers of nodavirus RNA2 (RNA2) and secretory-IgM mRNA (sec-igmicro) in the eye, brain, mid/posterior kidney and spleen sampled over a period of 81 days. In the eye and brain, levels of both RNA2 and sec-igmicro increased significantly early in the infection. In the spleen and mid/posterior kidney, both RNA2 and sec-igmicro were detected but the levels remained unchanged during the experimental period. The levels of RNA2 and sec-igmicro in the eye and brain were strongly correlated (P<0.0001). Nodavirus antigen was demonstrated by immunohistochemistry (IHC) in the retina of eyes from a relatively few fish from day 34 post challenge (brain not examined), but not at any time in the spleen and anterior kidney. By IHC, IgM+ cells were observed in conjunction with nodavirus positive IHC labelling in the retina. In both the spleen and anterior kidney, the number of IgM+ cells increased from day 3 post challenge. By conventional real-time RT-PCR, RNA2 was only sporadically demonstrated in the posterior intestine, heart and gills. ELISA analysis revealed a nodavirus specific antibody response in serum that was significant from day 18 post challenge. No clinical signs or mortality related to nodavirus infection were observed in the challenged halibut. The results suggest that the nodavirus infection induced a significant antibody response through activation of B-cells in the kidney and spleen, and involved a substantial migration of antibody-secreting cells to infected peripheral tissues. 相似文献