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81.
Florin L Alter H Gröne HJ Szabowski A Schütz G Angel P 《Genesis (New York, N.Y. : 2000)》2004,38(3):139-144
Loss-of-function approaches by the Cre/loxP technology have provided powerful tools for functional analyses of genes of interest expressed preferentially in a particular tissue. Here we describe the generation of transgenic mouse lines expressing Cre recombinase under the control of the promoter/enhancer unit of the gene for the alpha2 chain of collagen type I (Col1alpha2). As an expression vector, we used a P1-derived artificial chromosome (PAC), which harbors approximately 100 kb carrying the col1alpha2 gene. The improved coding sequence of the Cre recombinase was introduced to replace the first exon of col1alpha2. Cre expression was determined by immunohistochemistry and Cre-mediated onset of beta-galactosidase expression in ROSA26R-Cre reporter mice. In four analyzed transgenic lines, Cre recombinase was efficiently expressed during embryogenesis and in adult animals in cells of mesenchymal origin, such as dermal fibroblasts, mesenchymal cells of blood vessel walls, and cells in fibrous connective tissues surrounding internal organs. 相似文献
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84.
Heinz Harms Hans-Peter Koops Heike Martiny Michael Wullenweber 《Archives of microbiology》1981,128(3):280-281
Polydedral inclusion bodies were isolated from exponentially grown cells of Nitrosomonas spec. The bodies contained d-ribulose, 1,5-bisphosphate carboxylase. The specific activity of the enzyme was 0.0122 mol CO2 fixed per min per mg of protein. 相似文献
85.
Jun Wang Tobias Sinnberg Heike Niessner Rebecca Dölker Birgit Sauer Wolfgang E. Kempf Friedegund Meier Nick Leslie Birgit Schittek 《Pigment cell & melanoma research》2015,28(5):572-589
Inhibition of the mitogen‐activated protein kinase (MAPK) pathway is a major advance in the treatment of metastatic melanoma. However, its therapeutic success is limited by the rapid emergence of drug resistance. The insulin‐like growth factor‐1 receptor (IGF‐1R) is overexpressed in melanomas developing resistance toward the BRAFV600 inhibitor vemurafenib. Here, we show that hyperactivation of BRAF enhances IGF‐1R expression. In addition, the phosphatase activity of PTEN as well as heterocellular contact to stromal cells increases IGF‐1R expression in melanoma cells and enhances resistance to vemurafenib. Interestingly, PTEN‐negative melanoma cells escape IGF‐1R blockade by decreased expression of the receptor, implicating that only in melanoma patients with PTEN‐positive tumors treatment with IGF‐1R inhibitors would be a suitable strategy to combat therapy resistance. Our data emphasize the crosstalk and therapeutic relevance of microenvironmental and tumor cell‐autonomous mechanisms in regulating IGF‐1R expression and by this sensitivity toward targeted therapies. 相似文献
86.
Wahl M Link H Alexandridis N Thomason JC Cifuentes M Costello MJ da Gama BA Hillock K Hobday AJ Kaufmann MJ Keller S Kraufvelin P Krüger I Lauterbach L Antunes BL Molis M Nakaoka M Nyström J bin Radzi Z Stockhausen B Thiel M Vance T Weseloh A Whittle M Wiesmann L Wunderer L Yamakita T Lenz M 《PloS one》2011,6(5):e19514
Species richness is the most commonly used but controversial biodiversity metric in studies on aspects of community stability such as structural composition or productivity. The apparent ambiguity of theoretical and experimental findings may in part be due to experimental shortcomings and/or heterogeneity of scales and methods in earlier studies. This has led to an urgent call for improved and more realistic experiments. In a series of experiments replicated at a global scale we translocated several hundred marine hard bottom communities to new environments simulating a rapid but moderate environmental change. Subsequently, we measured their rate of compositional change (re-structuring) which in the great majority of cases represented a compositional convergence towards local communities. Re-structuring is driven by mortality of community components (original species) and establishment of new species in the changed environmental context. The rate of this re-structuring was then related to various system properties. We show that availability of free substratum relates negatively while taxon richness relates positively to structural persistence (i.e., no or slow re-structuring). Thus, when faced with environmental change, taxon-rich communities retain their original composition longer than taxon-poor communities. The effect of taxon richness, however, interacts with another aspect of diversity, functional richness. Indeed, taxon richness relates positively to persistence in functionally depauperate communities, but not in functionally diverse communities. The interaction between taxonomic and functional diversity with regard to the behaviour of communities exposed to environmental stress may help understand some of the seemingly contrasting findings of past research. 相似文献
87.
David A. Hughes Anke Hinney Harald Brumm Anne-Kathrin Wermter Heike Biebermann Johannes Hebebrand Mark Stoneking 《Human genetics》2009,124(6):633-647
The melanocortin 4 receptor (MC4R) is routinely investigated for the role it plays in human obesity, as mutations in MC4R are the most common dominantly inherited form of the disease. As little is known about the evolutionary history of this locus,
we investigated patterns of variation at MC4R in a worldwide sample of 1,015 humans from 51 populations, and in 8 central chimpanzees. There is a significant paucity of
diversity at MC4R in humans, but not in chimpanzees. The spectrum of mutations in humans, combined with the overall low level of diversity,
suggests that most (if not all) of the observed non-synonymous polymorphisms are likely to be transient deleterious mutations.
The MC4R coding region was resequenced in 12 primate species and sequences from an additional 29 vertebrates were included in molecular
evolutionary analyses. MC4R is highly conserved throughout vertebrate evolution, and has apparently been subject to high levels of continuous purifying
selection that increased approximately threefold during primate evolution. Furthermore, the strong selection extends to codon
usage bias, where most silent mutations are expected to be either quickly fixed or removed from the population, which may
help explain the unusually low levels of silent polymorphisms in humans. Finally, there is a significant tendency for non-synonymous
mutations that impact MC4R function to occur preferentially at sites that are identified by evolutionary analyses as being subject to very strong purifying
selection. The information from this study should help inform future epidemiological investigations of MC4R.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
88.
Susannetom Dieck Lydia Sanmartí-Vila Kristina Langnaese Karin Richter Stefan Kindler Antje Soyke Heike Wex Karl-Heinz Smalla Udo K?mpf Jürgen-Theodor Fr?nzer Markus Stumm Craig C. Garner Eckart D. Gundelfinger 《The Journal of cell biology》1998,142(2):499-509
The molecular architecture of the cytomatrix of presynaptic nerve terminals is poorly understood. Here we show that Bassoon, a novel protein of >400,000 M
r, is a new component of the presynaptic cytoskeleton. The murine bassoon gene maps to chromosome 9F. A comparison with the corresponding rat cDNA identified 10 exons within its protein-coding region. The Bassoon protein is predicted to contain two double-zinc fingers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, respectively). In some human proteins, e.g., Huntingtin, abnormal amplification of such poly-glutamine regions causes late-onset neurodegeneration. Bassoon is highly enriched in synaptic protein preparations. In cultured hippocampal neurons, Bassoon colocalizes with the synaptic vesicle protein synaptophysin and Piccolo, a presynaptic cytomatrix component. At the ultrastructural level, Bassoon is detected in axon terminals of hippocampal neurons where it is highly concentrated in the vicinity of the active zone. Immunogold labeling of synaptosomes revealed that Bassoon is associated with material interspersed between clear synaptic vesicles, and biochemical studies suggest a tight association with cytoskeletal structures. These data indicate that Bassoon is a strong candidate to be involved in cytomatrix organization at the site of neurotransmitter release. 相似文献
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90.
The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus 下载免费PDF全文
Laser H Conforti L Morreale G Mack TG Heyer M Haley JE Wishart TM Beirowski B Walker SA Haase G Celik A Adalbert R Wagner D Grumme D Ribchester RR Plomann M Coleman MP 《Molecular biology of the cell》2006,17(3):1075-1084
Slow Wallerian degeneration (Wld(S)) mutant mice express a chimeric nuclear protein that protects sick or injured axons from degeneration. The C-terminal region, derived from NAD(+) synthesizing enzyme Nmnat1, is reported to confer neuroprotection in vitro. However, an additional role for the N-terminal 70 amino acids (N70), derived from multiubiquitination factor Ube4b, has not been excluded. In wild-type Ube4b, N70 is part of a sequence essential for ubiquitination activity but its role is not understood. We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system. Interaction with Wld(S) targets VCP to discrete intranuclear foci where ubiquitin epitopes can also accumulate. Wld(S) lacking its N-terminal 16 amino acids (N16) neither binds nor redistributes VCP, but continues to accumulate in intranuclear foci, targeting its intrinsic NAD(+) synthesis activity to these same foci. Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues. We conclude that N-terminal sequences of Wld(S) protein influence the intranuclear location of both ubiquitin proteasome and NAD(+) synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP. 相似文献