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排序方式: 共有862条查询结果,搜索用时 15 毫秒
51.
Annina Kelloniemi Zoltan Szabo Raisa Serpi Juha N?p?nkangas Pauli Ohukainen Olli Tenhunen Leena Kaikkonen Elina Koivisto Zsolt Bagyura Risto Kerkel? Margret Leosdottir Thomas Hedner Olle Melander Heikki Ruskoaho Jaana Rys? 《PloS one》2015,10(6)
The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks’ follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio. 相似文献
52.
To many, the foundations of statistical inference are cryptic and irrelevant to routine statistical practice. The analysis of 2 x 2 contingency tables, omnipresent in the scientific literature, is a case in point. Fisher''s exact test is routinely used even though it has been fraught with controversy for over 70 years. The problem, not widely acknowledged, is that several different p-values can be associated with a single table, making scientific inference inconsistent. The root cause of this controversy lies in the table''s origins and the manner in which nuisance parameters are eliminated. However, fundamental statistical principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can shed light on the controversy and guide our approach in using this test. In this paper, we use these fundamental principles to show how much information is lost when the tables origins are ignored and when various approaches are used to eliminate unknown nuisance parameters. We present novel likelihood contours to aid in the visualization of information loss and show that the information loss is often virtually non-existent. We find that problems arising from the discreteness of the sample space are exacerbated by p-value-based inference. Accordingly, methods that are less sensitive to this discreteness - likelihood ratios, posterior probabilities and mid-p-values - lead to more consistent inferences. 相似文献
53.
Miia H. Vapola Aare Rokka Raija T. Sormunen Leena Alhonen Werner Schmitz Ernst Conzelmann Anni Wärri Silke Grunau Vasily D. Antonenkov J. Kalervo Hiltunen 《Developmental biology》2014
To understand the functional role of the peroxisomal membrane channel Pxmp2, mice with a targeted disruption of the Pxmp2 gene were generated. These mice were viable, grew and bred normally. However, Pxmp2−/− female mice were unable to nurse their pups. Lactating mammary gland epithelium displayed secretory lipid droplets and milk proteins, but the size of the ductal system was greatly reduced. Examination of mammary gland development revealed that retarded mammary ductal outgrowth was due to reduced proliferation of epithelial cells during puberty. Transplantation experiments established the Pxmp2−/− mammary stroma as a tissue responsible for suppression of epithelial growth. Morphological and biochemical examination confirmed the presence of peroxisomes in the mammary fat pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type mammary glands. Deletion of Pxmp2 led to an elevation in the expression of peroxisomal proteins in the mammary fat pad but not in liver or kidney of transgenic mice. Lipidomics of Pxmp2−/−mammary fat pad showed a decrease in the content of myristic acid (C14), a principal substrate for protein myristoylation and a potential peroxisomal β-oxidation product. Analysis of complex lipids revealed a reduced concentration of a variety of diacylglycerols and phospholipids containing mostly polyunsaturated fatty acids that may be caused by activation of lipid peroxidation. However, an antioxidant-containing diet did not stimulate mammary epithelial proliferation in Pxmp2−/− mice. 相似文献
54.
Erin N. Smith Wei Chen Mika K?h?nen Johannes Kettunen Terho Lehtim?ki Leena Peltonen Olli T. Raitakari Rany M. Salem Nicholas J. Schork Marian Shaw Sathanur R. Srinivasan Eric J. Topol Jorma S. Viikari Gerald S. Berenson Sarah S. Murray 《PLoS genetics》2010,6(9)
Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent genome-wide association (GWA) studies have pinpointed many loci associated with CVD risk factors in adults. It is unclear, however, if these loci predict trait levels at all ages, if they are associated with how a trait develops over time, or if they could be used to screen individuals who are pre-symptomatic to provide the opportunity for preventive measures before disease onset. We completed a genome-wide association study on participants in the longitudinal Bogalusa Heart Study (BHS) and have characterized the association between genetic factors and the development of CVD risk factors from childhood to adulthood. We report 7 genome-wide significant associations involving CVD risk factors, two of which have been previously reported. Top regions were tested for replication in the Young Finns Study (YF) and two associations strongly replicated: rs247616 in CETP with HDL levels (combined P = 9.7×10−24), and rs445925 at APOE with LDL levels (combined P = 8.7×10−19). We show that SNPs previously identified in adult cross-sectional studies tend to show age-independent effects in the BHS with effect sizes consistent with previous reports. Previously identified variants were associated with adult trait levels above and beyond those seen in childhood; however, variants with time-dependent effects were also promising predictors. This is the first GWA study to evaluate the role of common genetic variants in the development of CVD risk factors in children as they advance through adulthood and highlights the utility of using longitudinal studies to identify genetic predictors of adult traits in children. 相似文献
55.
Tompson SW Bacino CA Safina NP Bober MB Proud VK Funari T Wangler MF Nevarez L Ala-Kokko L Wilcox WR Eyre DR Krakow D Cohn DH 《American journal of human genetics》2010,87(5):708-712
Fibrochondrogenesis is a severe, autosomal-recessive, short-limbed skeletal dysplasia. In a single case of fibrochondrogenesis, whole-genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions. Because of the predominantly skeletal nature of the phenotype, the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage-selective genes via the UCLA Gene Expression Tool, UGET. The gene encoding the α1 chain of type XI collagen (COL11A1) was the only cartilage-selective gene among the three candidate intervals. Sequence analysis of COL11A1 in two genetically independent fibrochondrogenesis cases demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved triple-helical glycine residue on the other. The parents who were carriers of missense mutations had myopia. Early-onset hearing loss was noted in both parents who carried a loss-of-function allele, suggesting COL11A1 as a locus for mild, dominantly inherited hearing loss. These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers. 相似文献
56.
Background
One of the major challenges in the field of vaccine design is to predict conformational B-cell epitopes in an antigen. In the past, several methods have been developed for predicting conformational B-cell epitopes in an antigen from its tertiary structure. This is the first attempt in this area to predict conformational B-cell epitope in an antigen from its amino acid sequence.Results
All Support vector machine (SVM) models were trained and tested on 187 non-redundant protein chains consisting of 2261 antibody interacting residues of B-cell epitopes. Models have been developed using binary profile of pattern (BPP) and physiochemical profile of patterns (PPP) and achieved a maximum MCC of 0.22 and 0.17 respectively. In this study, for the first time SVM model has been developed using composition profile of patterns (CPP) and achieved a maximum MCC of 0.73 with accuracy 86.59%. We compare our CPP based model with existing structure based methods and observed that our sequence based model is as good as structure based methods.Conclusion
This study demonstrates that prediction of conformational B-cell epitope in an antigen is possible from is primary sequence. This study will be very useful in predicting conformational B-cell epitopes in antigens whose tertiary structures are not available. A web server CBTOPE has been developed for predicting B-cell epitope http://www.imtech.res.in/raghava/cbtope/. 相似文献57.
Uddin MJ Schulte MI Maddukuri L Harp J Marnett LJ 《Nucleosides, nucleotides & nucleic acids》2010,29(11):831-840
An efficient enzymatic synthesis of 6-chloropurine-2'-deoxyriboside from the reaction of 6-chloropurine with 2'-deoxycytidine catalyzed by nucleoside-2'-deoxyribosyltransferase (E.C. 2.4.2.6) followed by chemical conversion into the 5'-dimethoxytrityl 3'-(2-cyanoethyl-N,N-diisopropylamino) phosphoramidite derivative is described. The phosphoramidite derivative was incorporated site-specifically into an oligonucleotide and used for the introduction of a tethered tetramethylrhodamine-cadaverine conjugate. The availability of an efficient route to 6-chloropurine-2'-deoxyriboside 5'-dimethoxytrityl 3'-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidite enables the facile synthesis of oligonucleotides containing a range of functional groups tethered to deoxyadenosine residues. 相似文献
58.
Extracellular human granulocyte-macrophage colony stimulating factor (hGM-CSF) expression was studied under the control of
the GAP promoter in recombinant Pichia pastoris in a series of continuous culture runs (dilution rates from 0.025 to 0.2 h−1). The inlet feed concentration was also varied and the steady state biomass concentration increased proportionally demonstrating
efficient substrate utilization and constancy of the biomass yield coefficient (Yx/s) for a given dilution rate. The specific product formation rate (qP) showed a strong correlation with dilution rates demonstrating growth associated product formation of hGM-CSF. The volumetric
product concentration achieved at the highest feed concentration (4×) and a dilution rate of 0.2 h−1 was 82 mg l−1 which was 5-fold higher compared to the continuous culture run with 1× feed concentration at the lowest dilution rate thus
translating to a 40 fold increase in the volumetric productivity. The specific product yield (YP/X) increased slightly from 2 to 2.5 mg g−1, with increasing dilution rates, while it remained fairly invariant, for all feed concentrations demonstrating negligible
product degradation or feed back inhibition. The robust nature of this expression system would make it easily amenable to
scale up for industrial production. 相似文献
59.
Polyploidization has been suggested as one of the most common mechanisms for plant diversification. It is often associated
with changes in several morphological, phenological and ecological plant traits, and therefore has the potential to alter
insect–plant interactions. Nevertheless, studies evaluating the effect of plant polyploidy on interspecific interactions are
still few. We investigated pre-dispersal seed predation by the butterfly Anthocharis cardamines in 195 populations of two ploidy levels of the herb Cardamine pratensis (tetraploid ssp. pratensis, 2n = 30 vs. octoploid ssp. paludosa, 2n = 56–64). We asked if differences in incidence and intensity of predation among populations were related to landscape characteristics,
plant ploidy level and population structure. The incidence of the seed predator increased with increasing plant population
size and decreasing distance to nearest population occupied by A. cardamines. The intensity of predation decreased with increasing plant population size and was not affected by isolation. Probability
of attack decreased with increasing shading, and intensity of predation was higher in grazed than in non-grazed habitats.
The attack intensity increased with increasing mean flower number of plant population, but was not affected by flowering phenology.
Individuals in tetraploid populations suffered on average from higher levels of seed predation, had higher mean flower number,
were less shaded and occurred more often in grazed habitats than octoploid populations. When accounting for differences in
habitat preferences between ploidy levels there was no longer a difference in intensity of predation, suggesting that the
observed differences in attack rates among populations of the two ploidy levels are mediated by the habitat. Overall, our
results suggest that polyploidization is associated with differentiation in habitat preferences and phenotypic traits leading
to differences in interspecific interaction among plant populations. This, in turn, may facilitate further divergence of ploidy
levels. 相似文献
60.