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Ezgi Kunttas-Tatli Ryan A. Von Kleeck Bradford D. Greaves David Vinson David M. Roberts Brooke M. McCartney 《Molecular biology of the cell》2015,26(24):4503-4518
The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC’s tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation–based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function. 相似文献
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Brooke A. Armfield J. Craig George Christopher J. Vinyard J. G. M. Thewissen 《Marine Mammal Science》2011,27(4):819-827
Unlike other mammals, odontocetes and mysticetes have highly derived craniofacial bones. A growth process referred to as “telescoping” is partly responsible for this morphology. Here, we explore how changes in facial morphology during fetal growth relate to differences in telescoping between the adult odontocete Stenella attenuata and the mysticete Balaena mysticetus. We conclude that in both Stenella and Balaena head size increases allometrically. Similarly, odontocete nasal length and mysticete mouth size have strong positive allometry compared to total body length. However, the differences between odontocetes and mysticetes in telescoping are not directly associated with their fetal growth patterns. Our results suggest that cranial changes related to echolocation and feeding between odontocetes and mysticetes, respectively, begin during ontogeny before telescoping is initiated. 相似文献
124.
Brooke R Snyder Pei-Hsun Cheng Jinjing Yang Shang-Hsun Yang Anderson HC Huang Anthony WS Chan 《BMC cell biology》2011,12(1):1-8
Background
Activation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors. High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive.Results
Here we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca2+)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca2+ concentration [Ca2+] difference between bulk cytosolic and the sub-plasma membrane rim.Conclusion
This approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane. Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation. Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process. 相似文献125.
Veronica A. Brown Anne Brooke James A. Fordyce Gary F. McCracken 《Conservation Genetics》2011,12(4):933-941
The Mariana flying fox (Pteropus mariannus) has suffered substantial decline in recent years. Taxonomic classification of P. mariannus has been inconsistent, with subspecies designations based mainly on geography and morphological variation within small sample
sizes. In this study, we examine relationships of P. mariannus across two island groups in the western Pacific Ocean. Microsatellite data and mitochondrial sequences, from D-loop, cytochrome
oxidase I, and cytochrome b, suggest that the population on the islands of Palau is genetically isolated from the populations
in the Mariana Islands. Our data confirm that the bats of Palau should be considered a separate conservation unit from the
bats of the Mariana Islands, supporting the current subspecies separation of these two populations. Our results also suggest
that there is gene flow among islands within the Mariana archipelago and that the bats on these islands, currently classified
as two subspecies, should be managed as a single conservation unit, although we refrain from suggesting taxonomic revisions
until genetic and morphological data become available from geographically intermediate populations. 相似文献
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We previously reported that a secreted glycoprotein YKL-40 acts as an angiogenic factor to promote breast cancer angiogenesis. However, its functional role in normal mammary gland development is poorly understood. Here we investigated its biophysiological activity in mammary epithelial development and mammary tissue morphogenesis. YKL-40 was expressed exclusively by ductal epithelial cells of parous and non-parous mammary tissue, but was dramatically up-regulated at the beginning of involution. To mimic ductal development and explore activity of elevated YKL-40 during mammary tissue regression in vivo, we grew a mammary epithelial cell line 76N MECs in a 3-D Matrigel system in the presence of lactogenic hormones including prolactin, hydrocortisone, and insulin. Treatment of 76N MECs with recombinant YKL-40 significantly inhibited acinar formation, luminal polarization, and secretion. YKL-40 also suppressed expression of E-cadherin but increased MMP-9 and cell motility, the crucial mechanisms that mediate mammary tissue remodeling during involution. In addition, engineering of 76N MECs with YKL-40 gene to express ectopic YKL-40 recapitulated the same activities as recombinant YKL-40 in the inhibition of cell differentiation. These results suggest that YKL-40-mediated inhibition of cell differentiation and polarization in the presence of lactogenic hormones may represent its important function during mammary tissue involution. Identification of this biophysiological property will enhance our understanding of its pathologic role in the later stage of breast cancer that is developed from poorly differentiated and highly invasive cells. 相似文献
130.
Beesley J Pickett HA Johnatty SE Dunning AM Chen X Li J Michailidou K Lu Y Rider DN Palmieri RT Stutz MD Lambrechts D Despierre E Lambrechts S Vergote I Chang-Claude J Nickels S Vrieling A Flesch-Janys D Wang-Gohrke S Eilber U Bogdanova N Antonenkova N Runnebaum IB Dörk T Goodman MT Lurie G Wilkens LR Matsuno RK Kiemeney LA Aben KK Marees T Massuger LF Fridley BL Vierkant RA Bandera EV Olson SH Orlow I Rodriguez-Rodriguez L Cook LS Le ND Brooks-Wilson A Kelemen LE Campbell I Gayther SA Ramus SJ 《PloS one》2011,6(9):e24987
Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity. 相似文献