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991.
Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK 下载免费PDF全文
Reichenberger E Tiziani V Watanabe S Park L Ueki Y Santanna C Baur ST Shiang R Grange DK Beighton P Gardner J Hamersma H Sellars S Ramesar R Lidral AC Sommer A Raposo do Amaral CM Gorlin RJ Mulliken JB Olsen BR 《American journal of human genetics》2001,68(6):1321-1326
Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones. Linkage studies mapped the locus for the autosomal dominant form of CMD to an approximately 5-cM interval on chromosome 5p, which is defined by recombinations between loci D5S810 and D5S1954. Mutational analysis of positional candidate genes was performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular matrix. The mutations are two in-frame deletions and one in-frame insertion caused by a splicing defect. All mutations cluster within seven amino acids in one of the six possible cytosolic domains of ANK. These results suggest that the mutated protein has a dominant negative effect on the function of ANK, since reduced levels of pyrophosphate in bone matrix are known to increase mineralization. 相似文献
992.
We used marine phytoplankton from mesocosms seeded with different zooplankton densities to study the impact of mesozooplankton on phytoplankton nutrient limitation. After 7 d of grazing (copepod mesocosms) or 9 d (appendicularian mesocosms) phytoplankton nutrient limitation was studied by enrichment bioassays. After removal of mesozooplankton, bioassay bottles received either no nutrients, phosphorus or nitrogen alone, or a combination of nitrogen and phosphorus and were incubated for 2 d. Phytoplankton reproductive rates in the bottles without nutrient addition were calculated after correction for grazing by ciliates and indicated increasing nitrogen limitation with increasing copepod abundance. No nutrient limitation was found in the appendicularian mesocosms. The increase of nutrient limitation with increasing copepod density seems to be mainly the result of a trophic cascade effect: Copepods released nanoplankton from ciliate grazing pressure, and thereby enhanced nitrogen exhaustion by nanophytoplankton and reduced nitrogen excretion by ciliates. Nitrogen sequestration in copepod biomass, the mechanism predicted by the ecological stoichiometry theory, seems to have been a weaker effect because there was only little copepod growth during the experiment. 相似文献
993.
In Drosophila, a single oocyte develops within a 16-cell germline cyst. Although all 16 cells initiate meiosis and undergo premeiotic S phase, only the oocyte retains its meiotic chromosome configuration and remains in the meiotic cycle. The other 15 cells in the cyst enter the endocycle and develop as polyploid nurse cells. A longstanding goal in the field has been to identify factors that are concentrated or activated in the oocyte, that promote meiotic progression and/or the establishment of the oocyte identity. We present the characterization of the missing oocyte gene, an excellent candidate for a gene directly involved in the differentiation of the oocyte nucleus. The missing oocyte gene encodes a highly conserved protein that preferentially accumulates in pro-oocyte nuclei in early prophase of meiosis I. In missing oocyte mutants, the oocyte enters the endocycle and develops as a polyploid nurse cell. Genetic interaction studies indicate that missing oocyte influences meiotic progression prior to pachytene and may interact with pathways that control DNA metabolism. Our data strongly suggest that the product of the missing oocyte gene acts in the oocyte nucleus to facilitate the execution of the unique cell cycle and developmental programs that produce the mature haploid gamete. 相似文献
994.
Wnt signaling and the regulation of stem cell function 总被引:20,自引:0,他引:20
Canonical Wnt signaling plays a crucial role in controlling cell expansion in many types of stem cells. Recent studies, however, demonstrated that Wnt is not only a general stem cell growth factor but can also influence cell lineage decisions in certain stem cell types by promoting specific fates at the expense of others. Thus, Wnt signaling elicits multiple functions in stem cells. Wnt activity appears to depend on cell-intrinsic properties that might change with time during development, thereby altering the cellular response to Wnt. Moreover, the spatial context of a stem cell also determines how the cell interprets Wnt signal activity, in that synergistic or antagonistic signaling pathways can modulate Wnt signaling. How a stem cell integrates Wnt and other signals and how such signaling networks regulate stem cell function on the molecular level remains to be elucidated. 相似文献
995.
Dung from calves treated with synthetic pyrethroids negatively influenced, in varying degrees, survival, reproduction and size of the common dung fly Neomyia cornicina (Fabricius). This was documented in assays where the coprophagous larvae and adults of N. cornicina were exposed to dung collected from calves dosed with topical preparations of deltamethrin, flumethrin, cyfluthrin, and alpha-cypermethrin. Larval mortality was significantly increased in dung collected up to at least seven days after treatment with deltamethrin, alpha-cypermethrin and cyfluthrin. Alpha-cypermethrin caused significant mortality of adults allowed to feed on moist dung. Nulliparous flies fed for six days on dung collected three days after treatment of calves with alpha-cypermethrin or deltamethrin showed little or no ovarian development. A tendency for a comparable effect with flumethrin was also observed. A connection between ovarian development and inhibition of feeding was indicated by the observation of significantly lowered excretion rates in flies exposed to residues of deltamethrin, alpha-cypermethrin and flumethrin. Larvae that survived exposure to dung from calves dosed with deltamethrin, alpha-cypermethrin, or cyfluthrin gave rise to smaller flies. The effect on adult fly size decreased when larvae were exposed to dung collected at longer times after treatment of the calves. Adult fly size was significantly reduced in dung collected up to 14 days (alpha-cypermethrin) or up to 28 days after treatment (deltamethrin and cyfluthrin). Fluctuating asymmetry of a wing vein character did not reflect the anticipated levels of exposure. The study strongly indicated that the use of synthetic pyrethroids affected the insect dung fauna and that such use may reduce dung decomposition. 相似文献
996.
The nematode even-skipped homolog vab-7 regulates gonad and vulva position in Pristionchus pacificus
In free-living nematodes, developmental processes like the formation of the vulva, can be studied at a cellular level. Cell lineage and ablation studies have been carried out in various nematode species and multiple changes in vulval patterning have been identified. In Pristionchus pacificus, vulva formation differs from Caenorhabditis elegans with respect to several autonomous and conditional aspects of cell fate specification. To understand the molecular basis of these evolutionary changes, we have performed a genetic analysis of vulva formation in P. pacificus. Here, we describe two mutants where the vulva is shifted posteriorly, affecting which precursor cells will form vulval tissue in P. pacificus. Mutant animals show a concomitant posterior displacement of the gonadal anchor cell, indicating that the gonad and the vulva are affected in a similar way. We show that mutations in the even-skipped homolog of nematodes, vab-7, cause these posterior displacements. In addition, cell ablation studies in the vab-7 mutant indicate that the altered position of the gonad not only changes the cell fate pattern but also the developmental competence of vulval precursor cells. Investigation of Cel-vab-7 mutant animals showed a similar but weaker vulva defective phenotype to the one described for Ppa-vab-7. 相似文献
997.
The invariant cell lineage of nematodes allows the formation of organ systems, like the egg-laying system, to be studied at a single cell level. The Caenorhabditis elegans egg-laying system is made up of the vulva, the mesodermal gonad and muscles and several neurons. The gonad plays a central role in patterning the underlying ectoderm to form the vulva and guiding the migration of the sex myoblasts to their final position. In Pristionchus pacificus, the egg-laying system is homologous to C. elegans, but comparative studies revealed several differences at the cellular and molecular levels during vulval formation. For example, the mesoblast M participates in lateral inhibition, a process that influences the fate of two vulval precursor cells. Here, we describe the M lineage in Pristionchus and show that both the dorsal and ventral M sublineages are involved in lateral inhibition. Mutations in the homeotic gene Ppa-mab-5 cause severe misspecification of the M lineage, resembling more the C. elegans Twist than the mab-5 phenotype. Ectopic differentiation of P8.p in Ppa-mab-5 results from at least two separate interactions between M and P8.p. Thus, interactions among the Pristionchus egg-laying system are complex, involving multiple cells of different tissues occurring over a distance. 相似文献
998.
Hong A Lee-Kong S Iida T Sugimura I Lilly MA 《Development (Cambridge, England)》2003,130(7):1235-1242
Animal oocytes undergo a highly conserved developmental arrest in prophase of meiosis I. Often this marks a period of rapid growth for the oocyte and is necessary to coordinate meiotic progression with the developmental events of oogenesis. In Drosophila, the oocyte develops within a 16-cell germline cyst. Throughout much of oogenesis, the oocyte remains in prophase of meiosis I. By contrast, its 15 mitotic sisters enter the endocycle and become polyploid in preparation for their role as nurse cells. How germline cysts establish and maintain these two independent cell cycles is unknown. We demonstrate a role for the p21(CIP)/p27(Kip1)/p57(Kip2)-like cyclin-dependent kinase inhibitor (cki) dacapo in the maintenance of the meiotic cycle in Drosophila oocytes. Our data indicate that it is through the differential regulation of the cki Dacapo that two modes of cell-cycle regulation are independently maintained within the common cytoplasm of ovarian cysts. 相似文献
999.
1000.
Over the past two to three decades, developmental biology has demonstrated that all multicellular organisms in the animal kingdom share many of the same molecular building blocks and many of the same regulatory genetic pathways. Yet we still do not understand how the various organisms use these molecules and pathways to assume all the forms we know today. Evolutionary developmental biology tackles this problem by comparing the development of one organism to another and comparing the genes involved and gene functions to understand what makes one organism different from another. In this review, we revisit a set of seven concepts defined by Lewis Wolpert (fate maps, asymmetric division, induction, competence, positional information, determination, and lateral inhibition) that describe the characters of many developmental systems and supplement them with three additional concepts (developmental genomics, genetic redundancy, and genetic networks). We will discuss examples of comparative developmental studies where these concepts have guided observations on the advent of a developmental novelty. Finally, we identify a set of evolutionary frameworks, such as developmental constraints, cooption, duplication, parallel and convergent evolution, and homoplasy, to adequately describe the evolutionary properties of developmental systems. 相似文献