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981.
982.
Reiss S Rebhan I Backes P Romero-Brey I Erfle H Matula P Kaderali L Poenisch M Blankenburg H Hiet MS Longerich T Diehl S Ramirez F Balla T Rohr K Kaul A Bühler S Pepperkok R Lengauer T Albrecht M Eils R Schirmacher P Lohmann V Bartenschlager R 《Cell host & microbe》2011,9(1):32-45
Hepatitis C virus (HCV) is a major causative agent of chronic liver disease in humans. To gain insight into host factor requirements for HCV replication, we performed a siRNA screen of the human kinome and identified 13 different kinases, including phosphatidylinositol-4 kinase III alpha (PI4KIIIα), as being required for HCV replication. Consistent with elevated levels of the PI4KIIIα product phosphatidylinositol-4-phosphate (PI4P) detected in HCV-infected cultured hepatocytes and liver tissue from chronic hepatitis C patients, the enzymatic activity of PI4KIIIα was critical for HCV replication. Viral nonstructural protein 5A (NS5A) was found to interact with PI4KIIIα and stimulate its kinase activity. The absence of PI4KIIIα activity induced a dramatic change in the ultrastructural morphology of the membranous HCV replication complex. Our analysis suggests that the direct activation of a lipid kinase by HCV NS5A contributes critically to the integrity of the membranous viral replication complex. 相似文献
983.
Roux M Schwessinger B Albrecht C Chinchilla D Jones A Holton N Malinovsky FG Tör M de Vries S Zipfel C 《The Plant cell》2011,23(6):2440-2455
Recognition of pathogen-associated molecular patterns (PAMPs) by surface-localized pattern recognition receptors (PRRs) constitutes an important layer of innate immunity in plants. The leucine-rich repeat (LRR) receptor kinases EF-TU RECEPTOR (EFR) and FLAGELLIN SENSING2 (FLS2) are the PRRs for the peptide PAMPs elf18 and flg22, which are derived from bacterial EF-Tu and flagellin, respectively. Using coimmunoprecipitation and mass spectrometry analyses, we demonstrated that EFR and FLS2 undergo ligand-induced heteromerization in planta with several LRR receptor-like kinases that belong to the SOMATIC-EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) family, including BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1/SERK3 (BAK1/SERK3) and BAK1-LIKE1/SERK4 (BKK1/SERK4). Using a novel bak1 allele that does not exhibit pleiotropic defects in brassinosteroid and cell death responses, we determined that BAK1 and BKK1 cooperate genetically to achieve full signaling capability in response to elf18 and flg22 and to the damage-associated molecular pattern AtPep1. Furthermore, we demonstrated that BAK1 and BKK1 contribute to disease resistance against the hemibiotrophic bacterium Pseudomonas syringae and the obligate biotrophic oomycete Hyaloperonospora arabidopsidis. Our work reveals that the establishment of PAMP-triggered immunity (PTI) relies on the rapid ligand-induced recruitment of multiple SERKs within PRR complexes and provides insight into the early PTI signaling events underlying this important layer of plant innate immunity. 相似文献
984.
985.
Albrecht P Müller AK Südmeyer M Ferrea S Ringelstein M Cohn E Aktas O Dietlein T Lappas A Foerster A Hartung HP Schnitzler A Methner A 《PloS one》2012,7(4):e34891
Background/Objective
Parkinson''s disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases.Methods
This cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls.Results
The mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%.Conclusion
Different parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes. 相似文献986.
Boraska V Day-Williams A Franklin CS Elliott KS Panoutsopoulou K Tachmazidou I Albrecht E Bandinelli S Beilin LJ Bochud M Cadby G Ernst F Evans DM Hayward C Hicks AA Huffman J Huth C James AL Klopp N Kolcic I Kutalik Z Lawlor DA Musk AW Pehlic M Pennell CE Perry JR Peters A Polasek O St Pourcain B Ring SM Salvi E Schipf S Staessen JA Teumer A Timpson N Vitart V Warrington NM Yaghootkar H Zemunik T Zgaga L An P Anttila V Borecki IB Holmen J Ntalla I Palotie A Pietiläinen KH Wedenoja J 《PloS one》2012,7(3):e31369
Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC. 相似文献
987.
Jana Albrechtová Tomá? Albrecht Stuart J. E. Baird Milo? Macholán Geir Rudolfsen Pavel Munclinger Priscilla K. Tucker Jaroslav Piálek 《Proceedings. Biological sciences / The Royal Society》2012,279(1748):4803-4810
The house mouse hybrid zone (HMHZ) is a species barrier thought to be maintained by a balance between dispersal and natural selection against hybrids. While the HMHZ is characterized by frequency discontinuities for some sex chromosome markers, there is an unexpected large-scale regional introgression of a Y chromosome across the barrier, in defiance of Haldane''s rule. Recent work suggests that a major force maintaining the species barrier acts through sperm traits. Here, we test whether the Y chromosome penetration of the species barrier acts through sperm traits by assessing sperm characteristics of wild-caught males directly in a field laboratory set up in a Y introgression region of the HMHZ, later calculating the hybrid index of each male using 1401 diagnostic single nucleotide polymorphisms (SNPs). We found that both sperm count (SC) and sperm velocity were significantly reduced across the natural spectrum of hybrids. However, SC was more than rescued in the presence of the invading Y. Our results imply an asymmetric advantage for Y chromosome introgression consistent with the observed large-scale introgression. We suggest that selection on sperm-related traits probably explains a large component of patterns observed in the natural hybrid zone, including the Y chromosome penetration. 相似文献
988.
Grieder C Dhillon BS Schipprack W Melchinger AE 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(6):971-980
Biofuels have gained importance recently and the use of maize biomass as substrate in biogas plants for production of methane
has increased tremendously in Germany. The objectives of our research were to (1) estimate variance components and heritability
for different traits relevant to biogas production in testcrosses (TCs) of maize, (2) study correlations among traits, and
(3) discuss strategies to breed maize as a substrate for biogas fermenters. We evaluated 570 TCs of 285 diverse dent maize
lines crossed with two flint single-cross testers in six environments. Data were recorded on agronomic and quality traits,
including dry matter yield (DMY), methane fermentation yield (MFY), and methane yield (MY), the product of DMY and MFY, as
the main target trait. Estimates of variance components showed general combining ability (GCA) to be the major source of variation.
Estimates of heritability exceeded 0.67 for all traits and were even much greater in most instances. Methane yield was perfectly
correlated with DMY but not with MFY, indicating that variation in MY is primarily determined by DMY. Further, DMY had a larger
heritability and coefficient of genetic variation than MFY. Hence, for improving MY, selection should primarily focus on DMY
rather than MFY. Further, maize breeding for biogas production may diverge from that for forage production because in the
former case, quality traits seem to be of much lower importance. 相似文献
989.
Grieder C Dhillon BS Schipprack W Melchinger AE 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,124(6):981-988
Breeding maize for use as a biogas substrate (biogas maize) has recently gained considerable importance. To optimize hybrid
breeding programs, information about line per se performance (LP) of inbreds and its relation to their general combining ability
(GCA) is required. The objectives of our research were to (1) estimate variance components and heritability of LP for agronomic
and quality traits relevant to biogas production, (2) study correlations among traits as well as between LP and GCA, and (3)
discuss implications for breeding of biogas maize. We evaluated 285 diverse dent maize inbred lines in six environments. Data
were recorded on agronomic and quality traits, including dry matter yield (DMY), methane fermentation yield (MFY), and their
product, methane yield (MY), as the main target trait. In agreement with observations made for GCA in a companion study, variation
in MY was mainly determined by DMY. MFY, which showed moderate correlation with lignin but only weak correlation with starch,
revealed only low genotypic variation. Thus, our results favor selection of genotypes with high DMY and less focus on ear
proportion for biogas maize. Genotypic correlations between LP and GCA [r
g (LP, GCA)] were highest (≥0.94) for maturity traits (days to silking, dry matter concentration) and moderate (≥0.65) for
DMY and MY. Multistage selection is recommended. Selection for GCA of maturity traits, plant height, and to some extent also
quality traits and DMY on the level of LP looks promising. 相似文献
990.
Clostridium aminobutyricum ferments 4-aminobutyrate (γ-aminobutyrate, GABA) to ammonia, acetate and butyrate via 4-hydroxybutyrate that is activated
to the CoA-thioester catalyzed by 4-hydroxybutyrate CoA-transferase. Then, 4-hydroxybutyryl-CoA is dehydrated to crotonyl-CoA,
which disproportionates to butyryl-CoA and acetyl-CoA. Cocrystallization of the CoA-transferase with the alternate substrate
butyryl-CoA yielded crystals with non-covalently bound CoA and two water molecules at the active site. Most likely, butyryl-CoA
reacted with the active site Glu238 to CoA and the mixed anhydride, which slowly hydrolyzed during crystallization. The structure
of the CoA is similar but less stretched than that of the CoA-moiety of the covalent enzyme-CoA-thioester in 4-hydroxybutyrate
CoA-transferase from Shewanella oneidensis. In contrast to the structures of the apo-enzyme and enzyme-CoA-thioester, the structure described here has a closed conformation,
probably caused by a flip of the active site loop (residues 215–219). During turnover, the closed conformation may protect
the anhydride intermediate from hydrolysis and CoA from dissociation from the enzyme. Hence, one catalytic cycle changes conformation
of the enzyme four times: free enzyme—open conformation, CoA+ anhydride 1—closed, enzyme-CoA-thioester—open, CoA + anhydride-2—closed,
free enzyme—open. 相似文献