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991.
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993.
Spencer JR Sendzik M Oeh J Sabbatini P Dalrymple SA Magill C Kim HM Zhang P Squires N Moss KG Sukbuntherng J Graupe D Eksterowicz J Young PR Myers AG Green MJ 《Bioorganic & medicinal chemistry letters》2006,16(18):4884-4888
Novel analogs of (-)-saframycin A are described. The analogs are shown to be potent inhibitors of the in vitro growth of several tumor cells in a broad panel and promising as leads for further optimization. The first in vivo studies in a solid tumor model (HCT-116) reveal potent antitumor activity with associated toxicity of daily administration. 相似文献
994.
Shaked-Mishan P Suter-Grotemeyer M Yoel-Almagor T Holland N Zilberstein D Rentsch D 《Molecular microbiology》2006,60(1):30-38
We describe the first functional and molecular characterization of an amino acid permease (LdAAP3) from the human parasitic protozoan Leishmania donovani, the causative agent of visceral leishmaniasis in humans. This permease contains 480 amino acids with 11 predicted trans-membrane domains. Expressing LdAAP3 in Saccharomyces cerevisiae mutants revealed that LdAAP3 codes for a high-affinity arginine transporter (Km 1.9 microM). LdAAP3 is highly specific for arginine as its transport was not inhibited by other amino acids or arginine-related compounds. Using green fluorescence protein (GFP) fused to the N-terminus of LdAAP3, this transporter was localized to the surface membrane of promastigotes. The GFP-LdAAP3 chimera mediated a threefold increase in arginine transport in promastigotes, indicating that it is active and confirmed that LdAAP3 codes for an arginine transporter in parasite cells as well. LdAAP3 is novel as it shares a high level of homology with amino acid permeases from other trypanosomatidae but almost none with permeases from other phyla. The results of this work suggest that LdAAP3 might play a role in host-parasite interaction. 相似文献
995.
Fgf8 is required for anterior heart field development 总被引:5,自引:0,他引:5
Ilagan R Abu-Issa R Brown D Yang YP Jiao K Schwartz RJ Klingensmith J Meyers EN 《Development (Cambridge, England)》2006,133(12):2435-2445
In the mouse embryo, the splanchnic mesodermal cells of the anterior heart field (AHF) migrate from the pharynx to contribute to the early myocardium of the outflow tract (OT) and right ventricle (RV). Recent studies have attempted to distinguish the AHF from other precardiac populations, and to determine the genetic and molecular mechanisms that regulate its development. Here, we have used an Fgf8lacZ allele to demonstrate that Fgf8 is expressed within the developing AHF. In addition, we use both a hypomorphic Fgf8 allele (Fgf8neo) and Cre-mediated gene ablation to show that Fgf8 is essential for the survival and proliferation of the AHF. Nkx2.5Cre is expressed in the AHF, primary heart tube and pharyngeal endoderm, while TnT-Cre is expressed only within the specified heart tube myocardium. Deletion of Fgf8 by Nkx2.5Cre results in a significant loss of the Nkx2.5Cre lineage and severe OT and RV truncations by E9.5, while the remaining heart chambers (left ventricle and atria) are grossly normal. These defects result from significant decreases in cell proliferation and aberrant cell death in both the pharyngeal endoderm and splanchnic mesoderm. By contrast, ablation of Fgf8 in the TnT-Cre domain does not result in OT or RV defects, providing strong evidence that Fgf8 expression is crucial in the pharyngeal endoderm and/or overlying splanchnic mesoderm of the AHF at a stage prior to heart tube elongation. Analysis of downstream signaling components, such as phosphorylated-Erk and Pea3, identifies the AHF splanchnic mesoderm itself as a target for Fgf8 signaling. 相似文献
996.
Wolff S Stöter M Giamas G Piesche M Henne-Bruns D Banting G Knippschild U 《FEBS letters》2006,580(27):6477-6484
In this study we identified snapin as an interaction partner of the CK1 isoform delta (CK1delta) in the yeast two-hybrid system and localized the interacting domains of both proteins. The interaction of CK1delta with snapin was confirmed by co-immunoprecipitation. Snapin was phosphorylated by CK1delta in vitro. Both proteins localized in close proximity in the perinuclear region, wherein snapin was found to associate with membranes of the Golgi apparatus. The identification of snapin as a new substrate of CK1delta points towards a possible function for CK1delta in modulating snapin specific functions. 相似文献
997.
998.
Ostner J Chalise MK Koenig A Launhardt K Nikolei J Podzuweit D Borries C 《American journal of primatology》2006,68(7):701-712
In species with a high risk of infanticide, a conflict of interest exists between the sexes over the amount of paternity information that is available to males. While females are expected to keep males unaware of their reproductive status in order to confuse paternity, selection should favor those male traits that enhance the males' assessment of female status and consequently of paternity probability. In Hanuman langurs (Semnopithecus entellus), a species that is extremely vulnerable to infanticide, females have been shown to successfully conceal the exact timing of ovulation from males--perhaps because they exhibit no sexual swelling and mate during all reproductive phases, including gestation. Nevertheless, it remains unclear whether males have hitherto unrecognized information about females' reproductive condition on a broader level that could still enhance male reproductive success. We investigated male assessment of female reproductive states in a population of wild Hanuman langurs as indicated by changes in male behavior, such as rates of copulations, anogenital inspections, and consortships, in relation to different female receptive periods (pregnant, fertile-nonconceptional, and conceptional). Our data indicate that males were able to discern qualitatively distinct reproductive states. Males were more interested in fertile than pregnant females, as indicated by higher copulation rates. Based on consortships, males distinguished fertile from nonfertile phases, as well as fertile, nonconceptional receptive periods from conceptional ones. Hanuman langur males are thus not as unaware of female reproductive condition as previously thought, supporting the idea of an ongoing battle of the sexes over paternity information. However, granting some knowledge while at the same time concealing the exact day of ovulation may also reflect a pure female strategy of balancing paternity concentration with paternity confusion, which is the most likely strategy in this system with high infanticide risk and male defense of infants. 相似文献
999.
Due to the accumulating evidence that suggests that numerous unhealthy conditions in the indoor environment are the result
of abnormal growth of the filamentous fungi (mold) in and on building surfaces it is necessary to accurately determine the
organisms responsible for these maladies and to identify them in an accurate and timely manner. Historically, identification
of filamentous fungal (mold) species has been based on morphological characteristics, both macroscopic and microscopic. These
methods may often be time consuming and inaccurate, necessitating the development of identification protocols that are rapid,
sensitive, and precise. To this end, we have devised a simple PAN-PCR approach which when coupled to cloning and sequencing
of the clones allows for the unambiguous identification of multiple fungal organisms. Universal primers are used to amplify
ribosomal DNA sequences which are then cloned and transformed into Escherichia coli. Individual clones are then sequenced and individual sequences analyzed and organisms identified. Using this method we were
capable of identifying Stachybotrys chartarum, Penicillium purpurogenum, Aspergillus sydowii, and Cladosporium cladosporioides from a mixed culture. This method was found to be rapid, highly specific, easy to perform, and cost effective. 相似文献
1000.
Peng X Grosse B Le Tiec B Nicolas V Delagebeaudeuf C Bedda T Decaens C Cassio D 《Cell and tissue research》2006,323(2):233-243
Few in vitro models expressing complex hepatocyte polarity are available. We used the unpolarized rat Fao cell line to isolate
the polarized WIF-B line. These complex rat-human hybrid cells form functional simple bile canaliculi. To obtain Fao-derived
polarized models with a simpler chromosome content and developed bile canaliculi, we employed two approaches. Partial success
was achieved with monochromosomal hybrids. As shown by the immunolocalization of apical, basolateral, and tight-junctional
proteins, monochromosomal hybrid 11-3 cells were polarized. They formed simple functional bile canaliculi and transiently
expressed the typical polarity of simple epithelial cells. One subclone blocked in this polarity state was isolated. A more
robust approach was provided by spheroid culture, a three-dimensional system that strengthens cell-cell contacts. Transient
spheroid culture induced irreversible polarization of Fao cells. This induction occurred in most spheroids (approximately
1% of the cells). From populations enriched in stably polarized cells, we generated new polarized cell models, designated
Can. Can 3-1 cells formed simple functional bile canaliculi when plated at high density. Regardless of plating density, Can 9
and Can 10 cells formed long tubular branched canaliculi competent for vectorial transport of organic anions and bile acids,
and involving several dozen adjacent cells. Thus, we have generated new cell models stably expressing typical hepatocyte polarity.
Among these models, Can 9 and Can 10 are the first capable of forming functional, highly developed bile canaliculi similar
to those formed in vivo.
This work was supported by grants from the Association pour la Recherche sur le Cancer (no.6551), the Institut Curie (PIC
Signalisation Cellulaire, no. 914) and the Institut National de la Santé et de la Recherche Médicale (contract PRISME 98-09). 相似文献