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71.
Fu X Gharib SA Green PS Aitken ML Frazer DA Park DR Vaisar T Heinecke JW 《Journal of proteome research》2008,7(3):845-854
Detecting differentially expressed proteins is a key goal of proteomics. We describe a label-free method, the spectral index, for analyzing relative protein abundance in large-scale data sets derived from biological samples by shotgun proteomics. The spectral index is comprised of two biochemically plausible features: relative protein abundance (assessed by spectral counts) and the number of samples within a group with detectable peptides. We combined the spectral index with permutation analysis to establish confidence intervals for assessing differential protein expression in bronchoalveolar lavage fluid from cystic fibrosis and control subjects. Significant differences in protein abundance determined by the spectral index agreed well with independent biochemical measurements. When used to analyze simulated data sets, the spectral index outperformed four other statistical tests (Student's t-test, G-test, Bayesian t-test, and Significance Analysis of Microarrays) by correctly identifying the largest number of differentially expressed proteins. Correspondence analysis and functional annotation analysis indicated that the spectral index improves the identification of enriched proteins corresponding to clinical phenotypes. The spectral index is easily implemented and statistically robust, and its results are readily interpreted graphically. Therefore, it should be useful for biomarker discovery and comparisons of protein expression between normal and disease states. 相似文献
72.
Debby C. Barsi John E. Major Alex Mosseler Moira Campbell 《Trees - Structure and Function》2009,23(3):555-571
Chlorophyll pigment concentrations and proportions, nitrogen (N), and needle morphology traits, are important components of
growth and were examined in five hybrid index categories from controlled crosses of various crosstypes, ranging from pure
black spruce (BS) [Picea mariana (Mill.) B.S.P.] to pure red spruce (RS) (Picea rubens Sarg.) grown under controlled light and water environments. Black spruce had on average 10% greater total chlorophyll concentration
(CHL) than RS. Red spruce had proportionately less chlorophyll a:b and CHL:CAR (carotenoid) ratios than BS. Nitrogen (N) concentrations were 1.75 and 1.60% for BS and RS, respectively. Black
spruce had the lowest carbon (C):N ratio (29.7) and RS had among the highest (32.3). Interestingly, there was no difference
in specific needle area among hybrid indices. Most of the chlorophyll pigment, C and N traits followed an additive inheritance
model, evidenced by a near-linear relationship from BS to RS across hybrid indices. However, for CHL, CAR, and CHL:CAR ratio,
parental analysis showed significant male effects and non-significant female and male × female interaction effects. Black
spruce males had 15.1 and 9.6% higher CHL and CAR, respectively, than hybrid or RS males, thus showing an underlying paternally
inherited genetic control. Controlling for N differences, analysis of covariance (ANCOVA) showed that sun-grown seedlings
had 22.2% or 300 μg g−1 lower CHL than shade-grown seedlings. Controlling for N, ANCOVA showed that the drought-grown seedlings actually had 6.7%
or 100 μg g−1 greater CHL than the irrigated seedlings. Sun plus drought conditions gave the lowest CHL, N, and CHL:CAR ratio of all treatments,
showing an additive multi-stress effect. There was a significant hybrid index × light effect as a result of rank changes.
Sun-grown RS had the lowest CHL and N values, whereas shade-grown RS had among the highest CHL and N values. Red spruce are
at a competitive disadvantage compared with BS and most hybrid spruce in high light, high drought, and high light plus drought
conditions. Red spruce will be strongly limited in its distribution by successional opportunities resulting from prevalent
harvesting practices such as clearcutting. Silvicultural modifications and genetic restoration will be required to maintain
RS on the landscape of northeastern North America. 相似文献
73.
74.
Bakircioglu M Carvalho OP Khurshid M Cox JJ Tuysuz B Barak T Yilmaz S Caglayan O Dincer A Nicholas AK Quarrell O Springell K Karbani G Malik S Gannon C Sheridan E Crosier M Lisgo SN Lindsay S Bilguvar K Gergely F Gunel M Woods CG 《American journal of human genetics》2011,(5):543-535
We investigated three families whose offspring had extreme microcephaly at birth and profound mental retardation. Brain scans and postmortem data showed that affected individuals had brains less than 10% of expected size (≤10 standard deviation) and that in addition to a massive reduction in neuron production they displayed partially deficient cortical lamination (microlissencephaly). Other body systems were apparently unaffected and overall growth was normal. We found two distinct homozygous mutations of NDE1, c.83+1G>T (p.Ala29GlnfsX114) in a Turkish family and c.684_685del (p.Pro229TrpfsX85) in two families of Pakistani origin. Using patient cells, we found that c.83+1G>T led to the use of a novel splice site and to a frameshift after NDE1 exon 2. Transfection of tagged NDE1 constructs showed that the c.684_685del mutation resulted in a NDE1 that was unable to localize to the centrosome. By staining a patient-derived cell line that carried the c.83+1G>T mutation, we found that this endogeneously expressed mutated protein equally failed to localize to the centrosome. By examining human and mouse embryonic brains, we determined that NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. We show that NDE1 accumulates on the mitotic spindle of apical neural precursors in early neurogenesis. Thus, NDE1 deficiency causes both a severe failure of neurogenesis and a deficiency in cortical lamination. Our data further highlight the importance of the centrosome in multiple aspects of neurodevelopment. 相似文献
75.
Morrissey MB Ferguson MM 《Evolution; international journal of organic evolution》2011,65(4):1037-1047
In addition to the well-studied evolutionary parameters of (1) phenotype-fitness covariance and (2) the genetic basis of phenotypic variation, adaptive evolution by natural selection requires that (3) fitness variation is effected by heritable genetic differences among individuals and (4) phenotype-fitness covariances must be, at least in part, underlain by genetic covariances. These latter two requirements for adaptive evolutionary change are relatively unstudied in natural populations. Absence of the latter requirements could explain stasis of apparently directionally selected heritable traits. We provide complementary analyses of selection and variation at phenotypic and genetic levels for juvenile growth rate in brook charr Salvelinus fontinalis in Freshwater River, Newfoundland, Canada. Contrary to the vast majority of reports in fish, we found very little viability selection of juvenile body size. Large body size appears nonetheless to be selectively advantageous via a relationship with early maturity. Genetic patterns in evolutionary parameters largely reflected phenotypic patterns. We have provided inference of selection based on longitudinal data, which are uncommon in high fecundity organisms. Furthermore we have provided a practicable framework for further studies of the genetic basis of natural selection. 相似文献
76.
The glycosyl transferase encoded by the cellulose synthase-like gene CSLD3/KJK/RHD7 (At3g03050) is required for cell wall integrity during root hair formation in Arabidopsis thaliana but it remains unclear whether it contributes to the synthesis of cellulose or hemicellulose. We identified two new alleles,
root hair-defective (rhd) 7-1 and rhd7-4, which affect the C-terminal end of the encoded protein. Like root hairs in the previously characterized kjk-2 putative null mutant, rhd7-1 and rhd7-4 hairs rupture before tip growth but, depending on the growth medium and temperature, hairs are able to survive rupture and
initiate tip growth, indicating that these alleles retain some function. At 21°C, the rhd7 tip-growing root hairs continued to rupture but at 5oC, rupture was inhibited, resulting in long, wild type-like root hairs.
At both temperatures, the expression of another root hair-specific CSLD gene, CSLD2, was increased in the rhd7-4 mutant but reduced in the kjk-2 mutant, suggesting that CSLD2 expression is CSLD3-dependent, and that CSLD2 could partially compensate for CSLD3 defects to prevent rupture at 5°C. Using a fluorescent brightener
(FB 28) to detect cell wall (1 → 4)-β-glucans (primarily cellulose) and CCRC-M1 antibody to detect fucosylated xyloglucans
revealed a patchy distribution of both in the mutant root hair cell walls. Cell wall thickness varied, and immunogold electron
microscopy indicated that xyloglucan distribution was altered throughout the root hair cell walls. These cell wall defects
indicate that CSLD3 is required for the normal organization of both cellulose and xyloglucan in root hair cell walls. 相似文献
77.
Moira L. Steyn-Ross D. A. Steyn-Ross J. W. Sleigh M. T. Wilson 《Bulletin of mathematical biology》2011,73(2):398-416
When the brain is in its noncognitive “idling” state, functional MRI measurements reveal the activation of default cortical
networks whose activity is suppressed during cognitive processing. This default or background mode is characterized by ultra-slow
BOLD oscillations (∼0.05 Hz), signaling extremely slow cycling in cortical metabolic demand across distinct cortical regions.
Here we describe a model of the cortex which predicts that slow cycling of cortical activity can arise naturally as a result
of nonlinear interactions between temporal (Hopf) and spatial (Turing) instabilities. The Hopf instability is triggered by
delays in the inhibitory postsynaptic response, while the Turing instability is precipitated by increases in the strength
of the gap-junction coupling between interneurons. We comment on possible implications for slow dendritic computation and
information processing. 相似文献
78.
Wilke CM Wei S Wang L Kryczek I Kao J Zou W 《Cancer immunology, immunotherapy : CII》2011,60(11):1529-1541
It is generally thought that each cytokine exerts either immune stimulatory (inflammatory) or immune inhibitory (antiinflammatory
or regulatory) biological activities. However, multiple cytokines can enact both inhibitory and stimulatory effects on the
immune system. Two of these cytokines are interleukin (IL)-10 and interferon-gamma (IFNγ). IL-10 has demonstrated antitumor
immunity even though it has been known for years as an immunoregulatory protein. Generally perceived as an immune stimulatory
cytokine, IFNγ can also induce inhibitory molecule expression including B7-H1 (PD-L1), indoleamine 2,3-dioxygenase (IDO),
and arginase on multiple cell populations (dendritic cells, tumor cells, and vascular endothelial cells). In this review,
we will summarize current knowledge of the dual roles of both of these cytokines and stress the previously underappreciated
stimulatory role of IL-10 and inhibitory role of IFNγ in the context of malignancy. Our progressive understanding of the dual
effects of these cytokines is important for dissecting cytokine-associated pathology and provides new avenues for developing
effective immune therapy against human diseases, including cancer. 相似文献
79.
This paper describes a high yielding coupled enzymatic reaction using Bacillus halodurans purine nucleoside phosphorylase (PNP) and E. coli uridine phosphorylase (UP) for synthesis of 5-methyluridine (5-MU) by transglycosylation. Key parameters such as reaction temperature, pH, reactant loading, reactor configuration and enzyme loading were investigated. A guanosine conversion of 95% and a 5-MU yield of 85% were achieved at 1 l scale, with a productivity of 10 g l−1 h−1. 相似文献
80.
Sauane M Gopalkrishnan RV Sarkar D Su ZZ Lebedeva IV Dent P Pestka S Fisher PB 《Cytokine & growth factor reviews》2003,14(1):35-51
The melanoma differentiation-associated gene-7 (mda-7) was cloned by subtraction hybridization as a molecule whose expression is elevated in terminally differentiated human melanoma cells. Current information based on structural and sequence homology, has led to the recognition of MDA-7 as an IL-10 family cytokine member and its renaming as IL-24. Northern blot analysis revealed mda-7/IL-24 expression in human tissues associated with the immune system such as spleen, thymus, peripheral blood leukocytes and normal melanocytes. The MDA-7/IL-24 mouse counterpart, FISP, appears to be a Th2-specific protein and the rat counterpart, C49A/MOB-5, is associated with wound healing and is also induced as a consequence of ras-transformation. A notable property of MDA-7/IL-24 is its ability to induce apoptosis in a large spectrum of human cancer derived cell lines, in mouse xenografts and upon intratumoral injection in human tumors (phase I clinical trials). Various aspects of this intriguing molecule including its cytokine and anti-tumoral effects are described and discussed. 相似文献