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911.
Tony I. Venelinov John H. Beattie Jack R. Dainty Wendy J. Hollands Susan J. Fairweather-Tait Linda J. Harvey 《Journal of trace elements in medicine and biology》2007,21(2):138-140
To develop further our understanding of initial dietary copper metabolism, a method has been developed to separate plasma copper that is bound to albumin, from that bound to ceruloplasmin. This method has been tested using plasma samples from a pilot study involving six human volunteers who consumed 3mg oral doses of the stable isotope (65)Cu and gave blood samples at timed intervals up to 7 days. The results suggest that this method can be used to monitor dynamic fluctuations in newly absorbed copper over a short time frame. 相似文献
912.
Broad Complex (BRC) is an essential ecdysone-pathway gene required for entry into and progression through metamorphosis in Drosophila melanogaster. Mutations of three BRC complementation groups cause numerous phenotypes, including a common suite of morphogenesis defects involving central nervous
system (CNS), adult salivary glands (aSG), and male genitalia. These defects are phenocopied by the juvenile hormone mimic
methoprene. Four BRC isoforms are produced by alternative splicing of a protein-binding BTB/POZ-encoding exon (BTB
BRC
) to one of four tandemly duplicated, DNA-binding zinc-finger-encoding exons (Z1
BRC
, Z2
BRC
, Z3
BRC
, Z4
BRC
). Highly conserved orthologs of BTB
BRC
and all four Z
BRC
were found among published cDNA sequences or genome databases from Diptera, Lepidoptera, Hymenoptera, and Coleoptera, indicating
that BRC arose and underwent internal exon duplication before the split of holometabolous orders. Tramtrack subfamily members, abrupt, tramtrack, fruitless, longitudinals lacking (lola), and CG31666 were characterized throughout Holometabola and used to root phylogenetic analyses of Z
BRC
exons, which revealed that the Z
BRC
clade includes Z
abrupt
. All four Z
BRC
domains, including Z4
BRC
, which has no known essential function, are evolving in a manner consistent with selective constraint. We used transgenic
rescue to explore how different BRC isoforms contribute to shared tissue-morphogenesis functions. As predicted from earlier
studies, the common CNS and aSG phenotypes were rescued by BRC-Z1 in rbp mutants, BRC-Z2 in br mutants, and BRC-Z3 in 2Bc mutants. However, the isoforms are required at two different developmental stages, with BRC-Z2 and -Z3 required earlier than
BRC-Z1. The sequential action of BRC isoforms indicates subfunctionalization of duplicated Z
BRC
exons even when they contribute to common developmental processes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
913.
Borrelia burgdorferi, a causative agent of Lyme disease, has a highly unusual segmented genome composed of both circular molecules and linear DNA replicons terminated by covalently closed hairpin ends or telomeres. Replication intermediates of the linear molecules are processed into hairpin telomeres via the activity of ResT, a telomere resolvase. We report here the results of limited proteolysis and mass spectroscopy to identify two main structural domains in ResT, separated by a chymotrypsin cleavage site between residues 163 and 164 of the 449 amino acid protein. The two domains have been overexpressed and purified. DNA electrophoretic mobility shift assays revealed that the C-terminal domain (ResT(164-449)) displays sequence-specific DNA binding to the box 3,4,5 region of the telomere, while the N-terminal domain (ResT(1-163)) exhibits sequence-independent DNA binding activity. Further analysis by DNase I footprinting supports a model for telomere resolution in which the hairpin binding module of the N-terminal domain is delivered to the box 1,2 region of the telomere through its tethering to ResT(164-449). Conversely, ResT(1-164) may play an important regulatory role by modulating both sequence-specific DNA binding activity and catalysis by the C-terminal domain. 相似文献
914.
Notch signalling is needed to maintain, but not to initiate, the formation of prosensory patches in the chick inner ear 总被引:4,自引:0,他引:4
Notch signalling is well-known to mediate lateral inhibition in inner ear sensory patches, so as to generate a balanced mixture of sensory hair cells and supporting cells. Recently, however, we have found that ectopic Notch activity at an early stage can induce the formation of ectopic sensory patches. This suggests that Notch activity may have two different functions in normal ear development, acting first to promote the formation of the prosensory patches, and then later to regulate hair-cell production within the patches. The Notch ligand Serrate1 (Jag1 in mouse and humans) is expressed in the patches from an early stage and may provide Notch activation during the prosensory phase. Here, we test whether Notch signalling is actually required for prosensory patch development. When we block Notch activation in the chick embryo using the gamma-secretase inhibitor DAPT, we see a complete loss of prosensory epithelial cells in the anterior otocyst, where they are diverted into a neuroblast fate via failure of Delta1-dependent lateral inhibition. The cells of the posterior prosensory patch remain epithelial, but expression of Sox2 and Bmp4 is drastically reduced. Expression of Serrate1 here is initially almost normal, but subsequently regresses. The patches of sensory hair cells that eventually develop are few and small. We suggest that, in normal development, factors other than Notch activity initiate Serrate1 expression. Serrate1, by activating Notch, then drives the expression of Sox2 and Bmp4, as well as expression of the Serrate1 gene itself. The positive feedback maintains Notch activation and thereby preserves and perhaps extends the prosensory state, leading eventually to the development of normal sensory patches. 相似文献
915.
916.
Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile 下载免费PDF全文
Rossi L Salvetti A Marincola FM Lena A Deri P Mannini L Batistoni R Wang E Gremigni V 《Genome biology》2007,8(4):R62
Background
Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms. 相似文献917.
918.
SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity 总被引:3,自引:0,他引:3
Boström P Andersson L Rutberg M Perman J Lidberg U Johansson BR Fernandez-Rodriguez J Ericson J Nilsson T Borén J Olofsson SO 《Nature cell biology》2007,9(11):1286-1293
The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell. 相似文献
919.
Partridge L 《Aging cell》2007,6(5):595-598
The invertebrate model organisms continue to be engines of discovery in aging research. Recent work with Drosophila stem cells has thrown light on their human equivalents, and on the role of stem cells and their niches in the decline in fecundity with age. Inspired by observations of aging in bacteria and yeast, a new theoretical study has revealed evolutionary forces that could favour asymmetry in the distribution of damaged cell constituents at division, and hence pave the way for the evolution of aging and selective maintenance of integrity of the germ line. Mechanisms of nutrient sensing and cell signalling in the response of lifespan to dietary restriction have been elucidated. Powerful invertebrate models of human aging-related disease have been produced, and used to start to understand how the aging process acts as a risk factor for disease. In the near future, studies of invertebrate aging are likely to move away from an exclusive reliance on genetic manipulation towards a more biochemical and physiological understanding of these systems. 相似文献
920.
van der Heijde D Landewé R Boonen A Einstein S Herborn G Rau R Wassenberg S Weissman BN Winalski CS Sharp JT 《Arthritis research & therapy》2007,9(4):R62
The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine
which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method
detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest
at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded
whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified
Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel
agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately
assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse'
(78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features
were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts
were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent
readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All
22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired
images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent
project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size
was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features
to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or
was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers
applying the van der Heijde-modified Sharp scoring method and was reflected in their scores. 相似文献