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161.
162.
The DNA sequence of chromosome I of an African trypanosome: gene content,chromosome organisation,recombination and polymorphism 总被引:10,自引:1,他引:9 下载免费PDF全文
Hall N Berriman M Lennard NJ Harris BR Hertz-Fowler C Bart-Delabesse EN Gerrard CS Atkin RJ Barron AJ Bowman S Bray-Allen SP Bringaud F Clark LN Corton CH Cronin A Davies R Doggett J Fraser A Grüter E Hall S Harper AD Kay MP Leech V Mayes R Price C Quail MA Rabbinowitsch E Reitter C Rutherford K Sasse J Sharp S Shownkeen R MacLeod A Taylor S Tweedie A Turner CM Tait A Gull K Barrell B Melville SE 《Nucleic acids research》2003,31(16):4864-4873
The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99–100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters. 相似文献
163.
Sharp CD Hines I Houghton J Warren A Jackson TH Jawahar A Nanda A Elrod JW Long A Chi A Minagar A Alexander JS 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2592-H2598
l-Glutamate is a major excitatory neurotransmitter that binds ionotropic and metabotropic glutamate receptors. Cerebral endothelial cells from many species have been shown to express several forms of glutamate receptors; however, human cerebral endothelial cells have not been shown to express either the N-methyl-D-aspartate (NMDA) receptor message or protein. This study provides evidence that human cerebral endothelial cells express the message and protein for NMDA receptors. Human cerebral endothelial cell monolayer electrical resistance changes in response to glutamate receptor agonists, antagonists, and second message blockers were tested. RT-PCR and Western blot analysis were used to demonstrate the presence of the NMDA receptor. Glutamate and NMDA (1 mM) caused a significant decrease in electrical resistance compared with sham control at 2 h postexposure; this response could be blocked significantly by MK-801 (an NMDA antagonist), 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethyoxybenzoate (an intracellular Ca2+ antagonist), and N-acetyl-L-cystein (an antioxidant). Trans(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid, a metabotropic receptor agonist (1 mM), did not significantly decrease electrical resistance. Our results are consistent with a model where glutamate, at excitotoxic levels, may lead to a breakdown in the blood brain barrier via activation of NMDA receptors. 相似文献
164.
Safferling M Griffith H Jin J Sharp J De Jesus M Ng C Krulwich TA Wang DN 《Biochemistry》2003,42(47):13969-13976
The TetL antiporter from the Bacillus subtilis inner membrane is a tetracycline-divalent cation efflux protein that is energized by the electrochemical proton gradient across the membrane. In this study, we expressed tetL in Escherichia coli and investigated the oligomeric state of TetL in the membrane and in detergent solution. Evidence for an oligomeric state of TetL emerged from SDS-PAGE and Western blot analysis of membrane samples as well as purified protein samples from cells that expressed two differently tagged TetL species. Furthermore, no formation or restoration of TetL oligomers occurred upon detergent solubilization of the membrane. Rather, oligomeric forms established in vivo persisted after solubilization. Mass spectrometry of the purified protein showed the absence of proteolysis and posttranslational modifications. Analytical size-exclusion chromatography of the purified protein revealed a dimeric TetL in dodecyl-maltoside solution. In addition, TetL dimers were found in a number of other detergents and over a wide pH range. It is therefore likely that the oligomeric form of the protein in the membrane is also a dimer. 相似文献
165.
The maternal determinant VegT is required for both endoderm and mesoderm formation by the Xenopus embryo. An important downstream mediator of VegT action is Xsox17, which has been proposed to be induced in cell-autonomous, then signal-dependent phases. We show that Xsox17 is a direct VegT target, but that direct induction of Xsox17 by VegT is rapidly inhibited. This inhibition is relieved by TGF- beta signalling, to which the future endoderm cell is sensitised by VegT, resulting in the observed dependence on cell contact for maintained Xsox17 expression. We propose that this change in regulation is a consequence of a VegT-induced repressor, inhibiting direct induction of early endoderm markers by VegT, and contributing to the formation of the boundary of the endodermal domain. 相似文献
166.
167.
In vitro selection was used to sample SnRNA-related sequences for ribozyme activities, and several 2',5'-branch-forming ribozymes were isolated. One such ribozyme is highly dependent upon an 11-nt motif that contains a conserved U6 snRNA sequence (ACAGAGA-box) known to be important for pre-mRNA splicing. The ribozyme reaction is similar to the first step of splicing in that an internal 2'-hydroxyl of an unpaired adenosine attacks at the 5'-phosphate of a guanosine. It differs in that the leaving group is diphosphate rather than a 5' exon. The finding that lariat formation can be accomplished by a small RNA with sequences related to U6 snRNA indicates that the RNA available in the spliceosome may be involved in RNA-catalyzed branch formation. 相似文献
168.
Noda M Yamashita S Takahashi N Eto K Shen LM Izumi K Daniel S Tsubamoto Y Nemoto T Iino M Kasai H Sharp GW Kadowaki T 《The Journal of biological chemistry》2002,277(44):41817-41826
169.
Rudolph MJ Illig CR Subasinghe NL Wilson KJ Hoffman JB Randle T Green D Molloy CJ Soll RM Lewandowski F Zhang M Bone R Spurlino JC Deckman IC Manthey C Sharp C Maguire D Grasberger BL DesJarlais RL Zhou Z 《Bioorganic & medicinal chemistry letters》2002,12(3):491-495
A study of the S1 binding of lead 5-methylthiothiophene amidine 3, an inhibitor of urokinase-type plasminogen activator, was undertaken by the introduction of a variety of substituents at the thiophene 5-position. The 5-alkyl substituted and unsubstituted thiophenes were prepared using organolithium chemistry. Heteroatom substituents were introduced at the 5-position using a novel displacement reaction of 5-methylsulfonylthiophenes and the corresponding oxygen or sulfur anions. Small alkyl group substitution at the 5-position provided inhibitors equipotent with but possessing improved solubility. 相似文献
170.
The diverse consequences of different viral infections on the human population reflect both the history of their origins and the nature of their ongoing evolution. Advances in the ease of finding and characterizing viral genome sequences are having a major impact on our understanding of the diversity of human viruses and of their relatives infecting other species. 相似文献