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941.
Kato N Sakata T Breton G Le Roch KG Nagle A Andersen C Bursulaya B Henson K Johnson J Kumar KA Marr F Mason D McNamara C Plouffe D Ramachandran V Spooner M Tuntland T Zhou Y Peters EC Chatterjee A Schultz PG Ward GE Gray N Harper J Winzeler EA 《Nature chemical biology》2008,4(6):347-356
Calcium-dependent protein kinases play a crucial role in intracellular calcium signaling in plants, some algae and protozoa. In Plasmodium falciparum, calcium-dependent protein kinase 1 (PfCDPK1) is expressed during schizogony in the erythrocytic stage as well as in the sporozoite stage. It is coexpressed with genes that encode the parasite motor complex, a cellular component required for parasite invasion of host cells, parasite motility and potentially cytokinesis. A targeted gene-disruption approach demonstrated that pfcdpk1 seems to be essential for parasite viability. An in vitro biochemical screen using recombinant PfCDPK1 against a library of 20,000 compounds resulted in the identification of a series of structurally related 2,6,9-trisubstituted purines. Compound treatment caused sudden developmental arrest at the late schizont stage in P. falciparum and a large reduction in intracellular parasites in Toxoplasma gondii, which suggests a possible role for PfCDPK1 in regulation of parasite motility during egress and invasion. 相似文献
942.
943.
Neubert K Meister S Moser K Weisel F Maseda D Amann K Wiethe C Winkler TH Kalden JR Manz RA Voll RE 《Nature medicine》2008,14(7):748-755
Autoantibody-mediated diseases like myasthenia gravis, autoimmune hemolytic anemia and systemic lupus erythematosus represent a therapeutic challenge. In particular, long-lived plasma cells producing autoantibodies resist current therapeutic and experimental approaches. Recently, we showed that the sensitivity of myeloma cells toward proteasome inhibitors directly correlates with their immunoglobulin synthesis rates. Therefore, we hypothesized that normal plasma cells are also hypersensitive to proteasome inhibition owing to their extremely high amount of protein biosynthesis. Here we show that the proteasome inhibitor bortezomib, which is approved for the treatment of multiple myeloma, eliminates both short- and long-lived plasma cells by activation of the terminal unfolded protein response. Treatment with bortezomib depleted plasma cells producing antibodies to double-stranded DNA, eliminated autoantibody production, ameliorated glomerulonephritis and prolonged survival of two mouse strains with lupus-like disease, NZB/W F1 and MRL/lpr mice. Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases. 相似文献
944.
Aristides Moustakas Kerstin Wiegand Stephan Getzin David Ward Katrin M. Meyer Matthias Guenther Karl-Heinz Mueller 《Acta Oecologica》2008,33(3):355-364
Nearest tree neighbour distances and the tree spatial formation on a large scale over time and space replicates were examined. The study was conducted in a natural savanna ecosystem in the Southern Kalahari, South Africa. Nearest tree neighbour and point pattern analysis methods were used to investigate changes in the spatial pattern of trees in two plots. Trees larger than 2 m canopy diameter were mapped. We used aerial photographs of the study area from 1940, 1964, 1984, 1993, and a satellite image from 2001 to follow two plots over time. Field work was carried out too for classification accuracy. We were able to identify and individually follow over 2400 individual trees from 1940 until 2001. Nearest neighbour analysis results indicate that dead trees were on average closer to their nearest neighbouring trees than living trees were to their neighbours. Most dead trees were on average 6 m from their nearest neighbours, while most living trees were about 20 m apart. Point pattern analysis results show a cyclical transition from clumped to random and sequentially to regular tree spacing. These transitions were not correlated across two plots. Generally, decreases in small-scale clumping coincided with periods of high mortality. Our findings show that regular, clumped, and random tree pattern can occur, pending on time, location, and scale within the location. 相似文献
945.
Maier KC Godfrey JE Echeverri CJ Cheong FK Schroer TA 《Traffic (Copenhagen, Denmark)》2008,9(4):481-491
Dynactin is a highly conserved, multiprotein complex that works in conjunction with microtubule-based motors to power a variety of intracellular motile events. Dynamitin (p50) is a core element of dynactin structure. In the present study, we use targeted mutagenesis to evaluate how dynamitin's different structural domains contribute to its ability to self-associate, interact with dynactin and assemble into a complex with its close binding partner, p24. We show that these interactions involve three distinct structural elements: (i) a previously unidentified dimerization motif in the N-terminal 100 amino acids, (ii) an α-helical motif spanning aa 106–162 and (iii) the C-terminal half of the molecule (aa 213–406), which is predicted to fold into an antiparallel α-helix bundle. The N-terminal half of dynamitin by itself is sufficient to disrupt dynactin, although very high concentrations are required. The ability of mutations in dynamitin's interaction domains to disrupt dynactin in vitro was found to correlate with their inhibitory effects when expressed in cells. We determined that the dynactin subunit, p24, governs dynamitin oligomerization by binding dynamitin along its length. This suppresses aberrant multimerization and drives formation of a protein complex that is identical to the native dynactin shoulder. 相似文献
946.
Sørensen KK Kirk HG Olsson K Labouriau R Christiansen J 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2008,117(1):1-9
New potato (Solanum tuberosum) varieties are required to contain low levels of the toxic glycoalkaloids and a potential approach to obtain this is through marker-assisted selection (MAS). Before applying MAS it is necessary to map quantitative trait loci (QTLs) for glycoalkaloid content in potato tubers and identify markers that link tightly to this trait. In this study, tubers of a dihaploid BC(1) population, originating from a cross between 90-HAF-01 (S. tuberosum(1)) and 90-HAG-15 (S. tuberosum(2) x S. sparsipilum), were evaluated for content of alpha-solanine and alpha-chaconine (total glycoalkaloid, TGA) after field trials. In addition, tubers were assayed for TGA content after exposure to light. A detailed analysis of segregation patterns indicated that a major QTL is responsible for the TGA content in tubers of this potato population. One highly significant QTL was mapped to chromosome I of the HAG and the HAF parent. Quantitative trait loci for glycoalkaloid production in foliage of different Solanum species have previously been mapped to this chromosome. In the present research, QTLs for alpha-solanine and alpha-chaconine content were mapped to the same location as for TGA content. Similar results were observed for tubers exposed to light. The simple sequence repeat marker STM5136 was closely linked to the identified QTL. 相似文献
947.
Eastern Mediterranean sediments are characterized by the periodic occurrence of conspicuous, organic matter-rich sapropel
layers. Phylogenetic analysis of a large culture collection isolated from these sediments revealed that about one third of
the isolates belonged to the genus Photobacterium. In the present study, 22 of these strains were examined with respect to their phylogenetic and metabolic diversity. The
strains belonged to two distinct Photobacterium populations (Mediterranean cluster I and II). Strains of cluster I were isolated almost exclusively from organic-rich sapropel
layers and were closely affiliated with P. aplysiae (based on their 16S rRNA gene sequences). They possessed almost identical Enterobacterial Repetitive Intergenic Consensus
(ERIC) and substrate utilization patterns, even among strains from different sampling sites or from layers differing up to
100,000 years in age. Strains of cluster II originated from sapropels and from the surface and carbon-lean intermediate layers.
They were related to Photobacterium frigidiphilum but differed significantly in their fingerprint patterns and substrate spectra, even when these strains were obtained from
the same sampling site and layer. Temperature range for growth (4 to 33°C), salinity tolerance (5 to 100‰), pH requirements
(5.5–9.3), and the composition of polar membrane lipids were similar for both clusters. All strains grew by fermentation (glucose,
organic acids) and all but five by anaerobic respiration (nitrate, dimethyl sulfoxide, anthraquinone disulfonate, or humic
acids). These results indicate that the genus Photobacterium forms subsurface populations well adapted to life in the deep biosphere. 相似文献
948.
Chavarría-Krauser A Nagel KA Palme K Schurr U Walter A Scharr H 《The New phytologist》2008,177(3):811-821
Differential growth processes in root and shoot growth zones are governed by the transport kinetics of auxin and other plant hormones. While gene expression and protein localization of hormone transport facilitators are currently being unraveled using state-of-the-art techniques of live cell imaging, the quantitative analysis of growth reactions is lagging behind because of a lack of suitable methods. A noninvasive technique, based on digital image sequence processing, for visualizing and quantifying highly resolved spatio-temporal root growth processes was applied in the model plant Arabidopsis thaliana and was adapted to provide precise information on differential curvature production activity within the root growth zone. Comparison of root gravitropic curvature kinetics in wild-type and mutant plants altered in a facilitator for auxin translocation allowed the determination of differences in the location and in the temporal response of curvature along the growth zone between the investigated plant lines. The findings of the quantitative growth analysis performed here confirm the proposed action of the investigated transport facilitator. The procedure developed here for the investigation of differential growth processes is a valuable tool for characterizing the phenomenology of a wide range of shoot and root growth movements and hence facilitates elucidation of their molecular characterization. 相似文献
949.
Markert A Steffan N Ploss K Hellwig S Steiner U Drewke C Li SM Boland W Leistner E 《Plant physiology》2008,147(1):296-305
Ergoline alkaloids occur in taxonomically unrelated taxa, such as fungi, belonging to the phylum Ascomycetes and higher plants of the family Convolvulaceae. The disjointed occurrence can be explained by the observation that plant-associated epibiotic clavicipitalean fungi capable of synthesizing ergoline alkaloids colonize the adaxial leaf surface of certain Convolvulaceae plant species. The fungi are seed transmitted. Their capacity to synthesize ergoline alkaloids depends on the presence of an intact differentiated host plant (e.g. Ipomoea asarifolia or Turbina corymbosa [Convolvulaceae]). Here, we present independent proof that these fungi are equipped with genetic material responsible for ergoline alkaloid biosynthesis. The gene (dmaW) for the determinant step in ergoline alkaloid biosynthesis was shown to be part of a cluster involved in ergoline alkaloid formation. The dmaW gene was overexpressed in Saccharomyces cerevisiae, the encoded DmaW protein purified to homogeneity, and characterized. Neither the gene nor the biosynthetic capacity, however, was detectable in the intact I. asarifolia or the taxonomically related T. corymbosa host plants. Both plants, however, contained the ergoline alkaloids almost exclusively, whereas alkaloids are not detectable in the associated epibiotic fungi. This indicates that a transport system may exist translocating the alkaloids from the epibiotic fungus into the plant. The association between the fungus and the plant very likely is a symbiotum in which ergoline alkaloids play an essential role. 相似文献