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101.
Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh(-/-) males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm. 相似文献
102.
Michael Schmolke Volker Mohler Lorenz Hartl Friedrich J. Zeller Sai L. K. Hsam 《Molecular breeding : new strategies in plant improvement》2012,29(2):449-456
Powdery mildew is one of the most destructive foliar diseases of wheat. A set of differential Blumeria graminis f.sp. tritici (Bgt) isolates was used to test the powdery mildew response of a Triticum monococcum-derived resistant hexaploid line, Tm27d2. Segregation analysis of 95 F2:3 lines from a Chinese Spring/Tm27d2 cross revealed that the resistance of Tm27d2 is controlled by a single dominant gene.
Using monosomic analysis and a molecular mapping approach, the resistance gene was localized to the terminal end of chromosome
2AL. The linkage map of chromosome 2AL consisted of nine simple sequence repeat markers and one sequence-tagged site (STS)
marker (ResPm4) indicative for the Pm4 locus. According to the differential reactions of 19 wheat cultivars/lines with known powdery mildew resistance genes to
13 Bgt isolates, Tm27d2 carried a new resistance specificity. The complete association of the resistance allele with STS marker
ResPm4 indicated that it represented a new allele at the Pm4 locus. This new allele was designated Pm4d. The two flanking markers Xgwm526 and Xbarc122 closely linked to Pm4d at genetic distances of 3.4 and 1.0 cM, respectively, are present in chromosome bin 2AL1-0.85-1.00. 相似文献
103.
Gable A Qiu M Titus J Balchand S Ferenz NP Ma N Collins ES Fagerstrom C Ross JL Yang G Wadsworth P 《Molecular biology of the cell》2012,23(7):1254-1266
Kinesin-5 is an essential mitotic motor. However, how its spatial-temporal distribution is regulated in mitosis remains poorly understood. We expressed localization and affinity purification-tagged Eg5 from a mouse bacterial artificial chromosome (this construct was called mEg5) and found its distribution to be tightly regulated throughout mitosis. Fluorescence recovery after photobleaching analysis showed rapid Eg5 turnover throughout mitosis, which cannot be accounted for by microtubule turnover. Total internal reflection fluorescence microscopy and high-resolution, single-particle tracking revealed that mEg5 punctae on both astral and midzone microtubules rapidly bind and unbind. mEg5 punctae on midzone microtubules moved transiently both toward and away from spindle poles. In contrast, mEg5 punctae on astral microtubules moved transiently toward microtubule minus ends during early mitosis but switched to plus end-directed motion during anaphase. These observations explain the poleward accumulation of Eg5 in early mitosis and its redistribution in anaphase. Inhibition of dynein blocked mEg5 movement on astral microtubules, whereas depletion of the Eg5-binding protein TPX2 resulted in plus end-directed mEg5 movement. However, motion of Eg5 on midzone microtubules was not altered. Our results reveal differential and precise spatial and temporal regulation of Eg5 in the spindle mediated by dynein and TPX2. 相似文献
104.
Ippolito GC Hoi KH Reddy ST Carroll SM Ge X Rogosch T Zemlin M Shultz LD Ellington AD Vandenberg CL Georgiou G 《PloS one》2012,7(4):e35497
Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγnull engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγnull mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential DH-JH pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments. 相似文献
105.
Tzuu-fen Lee Sai Guna Ranjan Gurazada Jixian Zhai Shengben Li Stacey A. Simon Marjori A. Matzke Xuemei Chen Blake C. Meyers 《Epigenetics》2012,7(7):781-795
In plants, heterochromatin is maintained by a small RNA-based gene silencing mechanism known as RNA-directed DNA methylation (RdDM). RdDM requires the non-redundant functions of two plant-specific DNA-dependent RNA polymerases (RNAP), RNAP IV and RNAP V. RNAP IV plays a major role in siRNA biogenesis, while RNAP V may recruit DNA methylation machinery to target endogenous loci for silencing. Although small RNA-generating regions that are dependent on both RNAP IV and RNAP V have been identified previously, the genomic loci targeted by RNAP V for siRNA accumulation and silencing have not been described extensively. To characterize the RNAP V-dependent, heterochromatic siRNA-generating regions in the Arabidopsis genome, we deeply sequenced the small RNA populations of wild-type and RNAP V null mutant (nrpe1) plants. Our results showed that RNAP V-dependent siRNA-generating loci are associated predominately with short repetitive sequences in intergenic regions. Suppression of small RNA production from short repetitive sequences was also prominent in RdDM mutants including dms4, drd1, dms3 and rdm1, reflecting the known association of these RdDM effectors with RNAP V. The genomic regions targeted by RNAP V were small, with an estimated average length of 238 bp. Our results suggest that RNAP V affects siRNA production from genomic loci with features dissimilar to known RNAP IV-dependent loci. RNAP V, along with RNAP IV and DRM1/2, may target and silence a set of small, intergenic transposable elements located in dispersed genomic regions for silencing. Silencing at these loci may be actively reinforced by RdDM. 相似文献
106.
中国白条天牛属比较形态学研究(鞘翅目,天牛科,沟胫天牛亚科,白条天牛族) 总被引:1,自引:0,他引:1
比较研究了白条天牛属10种的外部形态特征.结果表明:颊、触角、前胸背板斑纹、鞘翅斑纹、鞘翅基部瘤突、中胸后侧片、前足第1跗节等外部形态特征在白条天牛属中具有种间分类学意义.上颚基部、腹部第7节腹板形状、触角长度可用于雌雄鉴别.通过比较云斑白条天牛Batocera lineolata Chevrolat,1852与多斑白条天牛Batocera horsfieldi(Hope,1839)的外部形态与雄性外生殖器特征,结果表明上述两种均为有效种. 相似文献
107.
David E. Volk Kurtis M. Anderson Sai H. A. Gandham Fiona J. May Li Li David W. C. Beasley Alan D. T. Barrett David G. Gorenstein 《Biomolecular NMR assignments》2008,2(2):155-157
Nearly complete backbone and side chain resonance assignments have been obtained for the third domain, residues M289–K400,
of the envelope protein from the sylvatic strain (P72–1244) of the dengue 1 virus, containing mutations N336S and E370K, using
double- and triple-resonance spectroscopy. 相似文献
108.
109.
Cao X Antonyuk SV Seetharaman SV Whitson LJ Taylor AB Holloway SP Strange RW Doucette PA Valentine JS Tiwari A Hayward LJ Padua S Cohlberg JA Hasnain SS Hart PJ 《The Journal of biological chemistry》2008,283(23):16169-16177
Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis. 相似文献
110.
Liang Y Pingali SV Jogalekar AS Snyder JP Thiyagarajan P Lynn DG 《Biochemistry》2008,47(38):10018-10026
Amino acid cross-strand pairing interactions along a beta-sheet surface have been implicated in protein beta-structural assembly and stability, yet the relative contributions have been difficult to evaluate directly. Here we develop the central core sequence of the Abeta peptide associated with Alzheimer's disease, Abeta(16-22), as an experimental system for evaluating these interactions. The peptide allows for internal comparisons between electrostatic and steric interactions within the beta-sheet and an evaluation of these cross-strand pair contributions to beta-sheet registry. A morphological transition from fibers to hollow nanotubes arises from changes in beta-sheet surface complementarity and provides a convenient indicator of the beta-strand strand registry. The intrinsic beta-sequence and pair correlations are critical to regulate secondary assembly. These studies provide evidence for a critical desolvation step that is not present in most models of the nucleation-dependent pathway for amyloid assembly. 相似文献