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131.
Nine newly described single-copy and lowcopy-number genomic DNA sequences isolated from a flow-sorted human Y chromosome library were mapped to regions of the human Y chromosome and were hybridized to Southern blots of male and female great ape genomic DNAs (Gorilla gorilla, Pan troglodytes, Pongo pygmaeus). Eight of the nine sequences mapped to the euchromatic Y long arm (Yq) in humans, and the ninth mapped to the short arm or pericentromeric region. All nine of the newly identified sequences and two additional human Yq sequences hybridized to restriction fragments in male but not female genomic DNA from the great apes, indicating Y chromosome localization. Seven of these 11 human Yq sequences hybridized to similarly-sized restriction endonuclease fragments in all the great ape species analyzed. The five human sequences that mapped to the most distal subregion of Yq (deletion of which region is associated with spermatogenic failure in humans) were hybridized to Southern blots generated by pulsed-field gel electrophoresis. These sequences define a region of approximately 1 Mb on human Yq in which HpaII tiny fragment (HTF) islands appear to be absent. The conservation of these human Yq sequences on great ape Y chromosomes indicates a greater stability in this region of the Y than has been previously described for most anonymous human Y chromosomal sequences. The stability of these sequences on great ape Y chromosomes seems remarkable given that this region of the Y does not undergo meiotic recombination and the sequences do not appear to encode genes for which positive selection might occur.
Correspondence to: B. Steele Allen 相似文献
132.
The association between bleomycin-induced chromatid aberrations and BUdR-label exchange between sister chromatids was investigated in order to evaluate Revell's exchange hypothesis for the formation of chromatid aberrations. The results of this study indicate that a larger than expected proportion of chromatid breaks can be accounted for by the exchange hypothesis though not all breaks are the result of incomplete exchange. 相似文献
133.
Molecular Genetic Analysis of Y-Chromosome Microdeletions in Men with Severe Spermatogenetic Defects
Loginova J. A. Nagornaya I. I. Shlikova S. A. Petrova L. I. Ribakova M. V. Kuznetsova T. V. Baranov V. S. 《Molecular Biology》2003,37(1):67-73
Microdeletions of the Y-chromosomal AZF loci were revealed in 10 (12%) of 82 patients with severe idiopathic spermatogenetic defects. Deletions involved AZFc in six patients, AZFa in one patient, AZFb+c in two patients, and AZFa+b+c in one patient. Microdeletion analysis employed multiplex PCR with 22 pairs of primers directed to Y-specific STS of deletion intervals 5, 6, and 7 (Yq11). Spermatogenesis in men with AZF microdeletions was assessed with semen analysis, microscopic examination of testicular aspirate, and quantitative karyotypic analysis of immature germline cells in ejaculate or aspirate. The character of spermatogenetic defects was correlated with the size and location of microdeletions in order to study the genotype–phenotype relationship. 相似文献
134.
Considerable progress has been made recently toward understanding the processes of mitochondrial DNA (mtDNA) damage and repair. However, a paucity of information still exists regarding the physiological effects of persistent mtDNA damage. This is due, in part, to experimental difficulties associated with targeting mtDNA for damage, while sparing nuclear DNA. Here, we characterize two systems designed for targeted mtDNA damage based on the inducible (Tet-ON) mitochondrial expression of the bacterial enzyme, exonuclease III, and the human enzyme, uracil-N-glyosylase containing the Y147A mutation. In both systems, damage was accompanied by degradation of mtDNA, which was detectable by 6 h after induction of mutant uracil-N-glycosylase and by 12 h after induction of exoIII. Unexpectedly, increases in the steady-state levels of single-strand lesions, which led to degradation, were small in absolute terms indicating that both abasic sites and single-strand gaps may be poorly tolerated in mtDNA. mtDNA degradation was accompanied by the loss of expression of mtDNA-encoded COX2. After withdrawal of the inducer, recovery from mtDNA depletion occurred faster in the system expressing exonuclease III, but in both systems reduced mtDNA levels persisted longer than 144 h after doxycycline withdrawal. mtDNA degradation was followed by reduction and loss of respiration, decreased membrane potential, reduced cell viability, reduced intrinsic reactive oxygen species production, slowed proliferation, and changes in mitochondrial morphology (fragmentation of the mitochondrial network, rounding and “foaming” of the mitochondria). The mutagenic effects of abasic sites in mtDNA were low, which indicates that damaged mtDNA molecules may be degraded if not rapidly repaired. This study establishes, for the first time, that mtDNA degradation can be a direct and immediate consequence of persistent mtDNA damage and that increased ROS production is not an invariant consequence of mtDNA damage. 相似文献
135.
136.
摘要 目的:探讨与研究前列环素(PGI)、神经肽Y(NPY)与冠状动脉临界病变的关系及对近期功能性心肌缺血的预测价值。方法:选择2018年8月到2021年9月本院诊治的80例冠状动脉临界病变患者与80例冠状动脉病变患者分别作为临界组与病例组,同期选择在本院体检的正常冠状动脉人群80例作为正常组,检测三组前列环素、神经肽Y表达水平并进行相关性分析。随访冠状动脉临界病变患者的近期预后并进行功能性心肌缺血的预测分析。结果:病例组、临界组的血清前列环素含量低于正常组,血清神经肽Y含量高于正常组,病例组与临界组对比有明显差异(P<0.05)。病例组、临界组的生理维度、社会维度、心理维度、环境维度等生命质量评分明显低于正常组,病例组也低于临界组(P<0.05)。在240例人群中,Pearson相关性分析显示血清前列环素、神经肽Y含量与冠状动脉临界病变的发生存在相关性(P<0.05)。多因素logistic回归分析显示前列环素、神经肽Y为导致冠状动脉临界病变发生的重要因素(P<0.05)。所有临界组患者预后随访到2022年4月,平均随访时间为31.02±2.58个月,发生功能性心肌缺血21例,发生率为26.3 %。接收者操作特征(ROC)曲线分析显示血清前列环素、神经肽Y预测功能性心肌缺血的曲线下面积分别为0.828、0.836。结论:冠状动脉临界病变患者多伴随有前列环素、神经肽Y表达异常,可导致生命质量下降,前列环素、神经肽Y与冠状动脉临界病变存在相关性,两者预测近期功能性心肌缺血的发生具有很好的价值。 相似文献
137.
P2Y receptors are G protein coupled receptors that respond to extracellular nucleotides to promote a multitude of signaling events. Our laboratory has purified several P2Y receptors with the goal of providing molecular insight into their: (1) ligand binding properties, (2) G protein signaling selectivities, and (3) regulation by RGS proteins and other signaling cohorts. The human P2Y1 receptor and the human P2Y12 receptor, both of which are intimately involved in ADP-mediated platelet aggregation, were purified to near homogeneity and studied in detail. After high-level expression from recombinant baculovirus infection of Sf9 insect cells, approximately 50% of the receptors were successfully extracted with digitonin. Purification of nearly homogeneous epitope-tagged P2Y receptor was achieved using metal-affinity chromatography followed by other traditional chromatographic steps. Yields of purified P2Y receptors range from 10 to 100 g/l of infected cells. Once purified, the receptors were reconstituted in model lipid vesicles along with their cognate G proteins to assess receptor function. Agonist-promoted increases in steady-state GTPase assays demonstrated the functional activity of the reconstituted purified receptor. We have utilized this reconstitution system to assess the action of various nucleotide agonists and antagonists, the relative G protein selectivity, and the influence of other proteins, such as phospholipase C, on P2Y receptor-promoted signaling. Furthermore, we have identified the RGS expression profile of platelets and have begun to assess the action of these RGS proteins in a reconstituted P2Y receptor/G protein platelet model. 相似文献
138.
Kejnovsky E Kubat Z Hobza R Lengerova M Sato S Tabata S Fukui K Matsunaga S Vyskot B 《Genetica》2006,128(1-3):167-175
Silene latifolia is a model dioecious plant with heteromorphic sex chromosomes. The Y chromosome is the largest in this species. Theoretical
models propose an accumulation of repetitive DNA sequences in non-recombining parts of the Y chromosome. In this study, we
isolated a BAC7H5 clone preferentially hybridizing to the Y chromosome of S. latifolia. Sequence analysis revealed that this BAC7H5 contains part of the chloroplast genome, indicating that these chloroplast sequences
have accumulated on the Y chromosome and also may contribute to its large size. We constructed Y chromosome- and X chromosome-specific
libraries and screened them to find Y- and/or X-linked copies of chloroplast sequences. Sequence analysis revealed higher
divergence of a non-genic region of the chloroplast sequences located on the Y chromosome while genic regions tested showed
only very low (max 0.9%) divergence from their chloroplast homologues. 相似文献
139.
The distribution of Alu and L1 retroelements in the human genome changes with their age. Active retroelements target AT-rich
regions, but their frequency increases in GC- and gene-rich regions of the genome with increasing age of the insertions. Currently
there is no consensus on the mechanism generating this pattern. In this paper we test the hypothesis that selection against
deleterious deletions caused by ectopic recombination between repeats is the main cause of the inhomogeneous distribution
of L1s and Alus, by means of a detailed analysis of the GC distribution of the repeats on the sex chromosomes. We show that
(1) unlike on the autosomes and X chromosome, L1s do not accumulate on the Y chromosome in GC-rich regions, whereas Alus accumulate
there to a minor extent; (2) on the Y chromosome Alu and L1 densities are positively correlated, unlike the negative correlation
on other chromosomes; and (3) in gene-poor regions of chromosome 4 and X, the distribution of Alus and L1s does not shift
toward GC-rich regions. In addition, we show that although local GC content of long L1 insertions is lower than average, their
selective loss from recombining chromosomes is not the main cause of the enrichment of ancient L1s in GC-rich regions. The
results support the hypothesis that ectopic recombination causes the shift of Alu and L1 distributions toward the gene-rich
regions of the genome.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
Reviewing Editor: Dr. Deborah Charlesworth 相似文献
140.
Gary W. Arendash William J. Millard Ralph Dawson Jr. Adrian J. Dunn Edwin M. Meyer 《Neurochemical research》1989,14(11):1113-1118
Young adult rats received either unilateral or bilateral ibotenic acid infusions in their nucleus basalis, destroying most of the cholinesterase-staining neurons in that region. Cerebral cortex levels of choline acetyltransferase, somatostatin, neuropeptide Y, and monoamines were then assayed 2.5 and 10 months after bilateral lesions, or, 2.5, 10, and 14 months after unilateral lesions. Entorhinal and cerebral cortex levels of several amino acid transmitters were also measured. As expected, choline acetyltransferase activity was decreased in the frontal cortex ipsilateral to the ibotenic acid infusion in unilaterally or bilaterally lesioned animals. Parietal cortex concentrations of somatostatin and neuropeptide Y were altered by lesioning in a complicated, time-dependent manner. Thus, while unilateral lesions transiently decreased or had no effect on these neuropeptide levels, bilateral lesions elevated the level of each neuropeptide by over 100% at 10 months. Other cortical transmitter systems investigated appeared to be less affected by nucleus basalis-lesions. Unilateral lesions had no effect on prefrontal cortex norepinephrine, serotonin, or dopamine content at 14 months post-lesioning. These different neurochemical effects of unilateral and bilateral nucleus basalis lesions may be important for developing a model for the trans-synaptic effects of cortical cholinergic deafferentation. 相似文献