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951.
Multifunctional genes are expected to evolve at lower rates because mutations in such genes that improve one function might often have deleterious effects on other functions. Here we tested for an association between multifunctionality and evolutionary rates in genes of Saccharomyces cerevisiae, and we find a highly significant negative correlation between the number of biological processes in which a gene is involved in and its rate of evolution. However, the magnitude of this effect is small, and the results do not support the notion that multifunctionality limits a gene's rate of evolution. 相似文献
952.
Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine 总被引:9,自引:2,他引:7
Schierack P Nordhoff M Pollmann M Weyrauch KD Amasheh S Lodemann U Jores J Tachu B Kleta S Blikslager A Tedin K Wieler LH 《Histochemistry and cell biology》2006,125(3):293-305
In vitro studies on the pathogenesis in swine have been hampered by the lack of relevant porcine cell lines. Since many bacterial
infections are swine-specific, studies on pathogenic mechanisms require appropriate cell lines of porcine origin. We have
characterized the permanent porcine intestinal epithelial cell line, IPEC-J2, using a variety of methods in order to assess
the usefulness of this cell line as an in vitro infection model. Electron microscopic analyses and histochemical staining
revealed the cells to be enterocyte-like with microvilli, tight junctions and glycocalyx-bound mucin. The functional integrity
of monolayers was determined by transepithelial electrical resistance (TEER) measurements. Both commensal bacteria and important
bacterial pathogens were chosen for study based on their principally different infection mechanisms: obligate extracellular
Escherichia coli, facultative intracellular Salmonella and obligate intracellular Chlamydia. We determined the colonization and proliferation of the bacteria on and within the host cells and monitored the host cell
response. We verified the expression of mRNAs encoding the cytokines IL-1α, −6, −7, −8, −18, TNF-α and GM-CSF, but not TGF-β
or MCP-1. IL-8 protein expression was enhanced by Salmonella invasion. We conclude that the IPEC-J2 cell line provides a relevant in vitro model system for porcine intestinal pathogen–host
cell interactions. 相似文献
953.
MCM proteins and DNA replication 总被引:15,自引:0,他引:15
The MCM proteins identify a group of ten conserved factors functioning in the replication of the genomes of archae and eukaryotic organisms. Among these, MCM2-7 proteins are related to each other and form a family of DNA helicases implicated at the initiation step of DNA synthesis. Recently this family expanded by the identification of two additional members that appear to be present only in multicellular organisms, MCM8 and MCM9. The function of MCM8 is distinct from that of MCM2-7 proteins, while the function of MCM9 is unknown. MCM1 and MCM10 are not related to this family, nor to each other, but also function in DNA synthesis. 相似文献
954.
Price DA Armour D de Groot M Leishman D Napier C Perros M Stammen BL Wood A 《Bioorganic & medicinal chemistry letters》2006,16(17):4633-4637
The discovery of maraviroc 17 is described with particular reference to the generation of high selectivity over affinity for the HERG potassium channel. This was achieved through the use of a high throughput binding assay for the HERG channel that is known to show an excellent correlation with functional effects. 相似文献
955.
Mamely I van Vugt MA Smits VA Semple JI Lemmens B Perrakis A Medema RH Freire R 《Current biology : CB》2006,16(19):1950-1955
DNA-damage checkpoints maintain genomic integrity by mediating a cell-cycle delay in response to genotoxic stress or stalled replication forks. In response to damage, the checkpoint kinase ATR phosphorylates and activates its effector kinase Chk1 in a process that critically depends on Claspin . However, it is not known how exactly this kinase cascade is silenced. Here we demonstrate that the abundance of Claspin is regulated through proteasomal degradation. In response to DNA damage, Claspin is transiently stabilized, and its expression depends on Chk1 kinase activity. In addition, we show that Claspin is degraded upon mitotic entry, a process that depends on the beta-TrCP-SCF ubiquitin ligase and Polo-like kinase-1 (Plk1). We demonstrate that Claspin interacts with both beta-TrCP and Plk1 and that inactivation of these components or the beta-TrCP recognition motif in Claspin prevents its mitotic degradation. Interestingly, expression of a nondegradable Claspin mutant inhibits recovery from a DNA-damage-induced checkpoint arrest. Thus, we conclude that Claspin levels are tightly regulated, both during unperturbed cell cycles and after DNA damage. Moreover, our data demonstrate that the degradation of Claspin at the onset of mitosis is an essential step for the recovery of a cell from a DNA-damage-induced cell-cycle arrest. 相似文献
956.
Consequences of constitutive and induced variation in plant nutritional quality for immune defence of a herbivore against parasitism 总被引:1,自引:0,他引:1
Tibor Bukovinszky Erik H. Poelman Rieta Gols Georgios Prekatsakis Louise E. M. Vet Jeffrey A. Harvey Marcel Dicke 《Oecologia》2009,160(2):299-308
The mechanisms through which trophic interactions between species are indirectly mediated by distant members in a food web
have received increasing attention in the field of ecology of multitrophic interactions. Scarcely studied aspects include
the effects of varying plant chemistry on herbivore immune defences against parasitoids. We investigated the effects of constitutive
and herbivore-induced variation in the nutritional quality of wild and cultivated populations of cabbage (Brassica oleracea) on the ability of small cabbage white Pieris rapae (Lepidoptera, Pieridae) larvae to encapsulate eggs of the parasitoid Cotesia glomerata (Hymenoptera, Braconidae). Average encapsulation rates in caterpillars parasitised as first instars were low and did not
differ among plant populations, with caterpillar weight positively correlating with the rates of encapsulation. When caterpillars
were parasitised as second instar larvae, encapsulation of eggs increased. Caterpillars were larger on the cultivated Brussels
sprouts plants and exhibited higher levels of encapsulation compared with caterpillars on plants of either of the wild cabbage
populations. Observed differences in encapsulation rates between plant populations could not be explained exclusively by differences
in host growth on the different Brassica populations. Previous herbivore damage resulted in a reduction in the larval weight of subsequent herbivores with a concomitant
reduction in encapsulation responses on both Brussels sprouts and wild cabbage plants. To our knowledge this is the first
study demonstrating that constitutive and herbivore-induced changes in plant chemistry act in concert, affecting the immune
response of herbivores to parasitism. We argue that plant-mediated immune responses of herbivores may be important in the
evaluation of fitness costs and benefits of herbivore diet on the third trophic level. 相似文献
957.
Marcel Walser Rene Pellaux Andreas Meyer Matthias Bechtold Herve Vanderschuren Richard Reinhardt Joseph Magyar Sven Panke Martin Held 《Nucleic acids research》2009,37(8):e57
We introduce a technology for the rapid identification and sequencing of conserved DNA elements employing a novel suspension array based on nanoliter (nl)-reactors made from alginate. The reactors have a volume of 35 nl and serve as reaction compartments during monoseptic growth of microbial library clones, colony lysis, thermocycling and screening for sequence motifs via semi-quantitative fluorescence analyses. nl-Reactors were kept in suspension during all high-throughput steps which allowed performing the protocol in a highly space-effective fashion and at negligible expenses of consumables and reagents. As a first application, 11 high-quality microsatellites for polymorphism studies in cassava were isolated and sequenced out of a library of 20 000 clones in 2 days. The technology is widely scalable and we envision that throughputs for nl-reactor based screenings can be increased up to 100 000 and more samples per day thereby efficiently complementing protocols based on established deep-sequencing technologies. 相似文献
958.
Federica Gigante Marcel Kaiser Reto Brun Ian H. Gilbert 《Bioorganic & medicinal chemistry》2009,17(16):5950-5961
There is an urgent need for the development of new drugs for the treatment of neglected tropical diseases such as human African trypanosomiasis, Chagas disease and leishmaniasis. Azasterols, have been shown to have activity against the parasites which cause these diseases. In this paper we report synthesis of new azasterols and subsequent analysis of the SAR. The chemistry focused on variations in the ester at the 3β-position of the sterol and the position of the nitrogen in the side chain. The data allowed us to derive preliminary pharmacophore models for the activity of the azasterols against the parasites which cause these diseases. 相似文献
959.