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961.
962.
963.
Bihari Z Pettkó-Szandtner A Csanádi G Balázs M Bartos P Kesseru P Kiss I Mécs I 《Zeitschrift für Naturforschung. C, Journal of biosciences》2007,62(3-4):285-295
Strain AR-46, isolated and identified as Acinetobacter haemolyticus, evolutionally distant from the known hydrocarbon-degrading Acinetobacter spp., proved to have excellent long-chain n-alkane-degrading ability. This is the first detailed report on an n-alkane-utilizing strain belonging to this species. The preferred substrate is n-hexadecane, with an optimal temperature of 37 degrees C under aerobic conditions. Five complete and two partial open reading frames were sequenced and correlated with the early steps of monoterminal oxidation-initiated n-alkane mineralization. The encoded protein sequences and the arrangement of these genes displayed high similarity to those found in Acinetobacter sp. M-1, but AR-46 seemed to have only one alkane hydroxylase gene, with a completely different induction profile. Unique behaviour was also observed in n-alkane bioavailability. Substrate uptake occurred through the hydrophobic surface of n-alkane droplet-adhered cells possessing long, thick fimbriae, which were presumed to play a major role in n-alkane solubilization. A majority of the cells was in detached form, with thick, but short fimbriae. These free cells were permanently hydrophilic, unlike the cells of other Acinetobacter strains. 相似文献
964.
Péter Sólymos 《Biodiversity and Conservation》2007,16(2):347-356
Legal instruments for species conservation have been criticised because they take a long time to draw up and implement and
because invertebrates are highly underrepresented. For these reasons legal documents need regular re-evaluation as more data
and effective methods are available. The effectiveness of the Hungarian legislative texts was assessed by the congruence between
protection status and conservation priority of the species. Species were prioritised according to the conservation priority
index (CPI = MRI × PBR), which included mollusca rarity index (MRI) and protection-by-reserves score (PBR). Mollusca rarity
index was an additive scoring method including global range size, local frequency, and a correction factor due to the biased
frequency estimate or special importance of some species. PBR scores expressed the lack of congruence between distribution
of reserves and distribution of species. I used the distribution data of 121 Hungarian land snail species based on 10 × 10
km resolution grid system. Current protection status of the species was associated with rarity, whereas the congruence between
species occurrences and the location of existing reserves has been overlooked. Based on the 25% of the species with highest
CPI scores, the species Helicigona planospira was highly recommended and 9 other species was recommended for protection. Two thirds of the occurrences of the strictly
protected and endemic species Hygromia kovacsi and more than 25% of the occurrences of 10 protected species were located outside of current reserves. Local populations
of these species need monitoring in order to detect changes in the area of occupancy. 相似文献
965.
The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1
Lénárt P Petronczki M Steegmaier M Di Fiore B Lipp JJ Hoffmann M Rettig WJ Kraut N Peters JM 《Current biology : CB》2007,17(4):304-315
BACKGROUND: The mitotic kinases, Cdk1, Aurora A/B, and Polo-like kinase 1 (Plk1) have been characterized extensively to further understanding of mitotic mechanisms and as potential targets for cancer therapy. Cdk1 and Aurora kinase studies have been facilitated by small-molecule inhibitors, but few if any potent Plk1 inhibitors have been identified. RESULTS: We describe the cellular effects of a novel compound, BI 2536, a potent and selective inhibitor of Plk1. The fact that BI 2536 blocks Plk1 activity fully and instantaneously enabled us to study controversial and unknown functions of Plk1. Cells treated with BI 2536 are delayed in prophase but eventually import Cdk1-cyclin B into the nucleus, enter prometaphase, and degrade cyclin A, although BI 2536 prevents degradation of the APC/C inhibitor Emi1. BI 2536-treated cells lack prophase microtubule asters and thus polymerize mitotic microtubules only after nuclear-envelope breakdown and form monopolar spindles that do not stably attach to kinetochores. Mad2 accumulates at kinetochores, and cells arrest with an activated spindle-assembly checkpoint. BI 2536 prevents Plk1's enrichment at kinetochores and centrosomes, and when added to metaphase cells, it induces detachment of microtubules from kinetochores and leads to spindle collapse. CONCLUSIONS: Our results suggest that Plk1's accumulation at centrosomes and kinetochores depends on its own activity and that this activity is required for maintaining centrosome and kinetochore function. Our data also show that Plk1 is not required for prophase entry, but delays transition to prometaphase, and that Emi1 destruction in prometaphase is not essential for APC/C-mediated cyclin A degradation. 相似文献
966.
BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo 总被引:9,自引:0,他引:9
Steegmaier M Hoffmann M Baum A Lénárt P Petronczki M Krssák M Gürtler U Garin-Chesa P Lieb S Quant J Grauert M Adolf GR Kraut N Peters JM Rettig WJ 《Current biology : CB》2007,17(4):316-322
Fine-mapping of the cell-division cycle, notably the identification of mitotic kinase signaling pathways, provides novel opportunities for cancer-drug discovery. As a key regulator of multiple steps during mitotic progression across eukaryotic species, the serine/threonine-specific Polo-like kinase 1 (Plk1) is highly expressed in malignant cells and serves as a negative prognostic marker in specific human cancer types . Here, we report the discovery of a potent small-molecule inhibitor of mammalian Plk1, BI 2536, which inhibits Plk1 enzyme activity at low nanomolar concentrations. The compound potently causes a mitotic arrest and induces apoptosis in human cancer cell lines of diverse tissue origin and oncogenome signature. BI 2536 inhibits growth of human tumor xenografts in nude mice and induces regression of large tumors with well-tolerated intravenous dose regimens. In treated tumors, cells arrest in prometaphase, accumulate phosphohistone H3, and contain aberrant mitotic spindles. This mitotic arrest is followed by a surge in apoptosis, detectable by immunohistochemistry and noninvasive optical and magnetic resonance imaging. For addressing the therapeutic potential of Plk1 inhibition, BI 2536 has progressed into clinical studies in patients with locally advanced or metastatic cancers. 相似文献
967.
ter Horst SA Walther FJ Poorthuis BJ Hiemstra PS Wagenaar GT 《American journal of physiology. Lung cellular and molecular physiology》2007,293(1):L35-L44
Administration of inhaled nitric oxide (iNO) is a potential therapeutic strategy to prevent bronchopulmonary dysplasia (BPD) in premature newborns with respiratory distress syndrome. We evaluated this approach in a rat model, in which premature pups were exposed to room air, hyperoxia, or a combination of hyperoxia and NO (8.5 and 17 ppm). We investigated the anti-inflammatory effects of prolonged iNO therapy by studying survival, histopathology, fibrin deposition, and differential mRNA expression (real-time RT-PCR) of key genes involved in the development of BPD. iNO therapy prolonged median survival 1.5 days (P = 0.0003), reduced fibrin deposition in a dosage-dependent way up to 4.3-fold (P < 0.001), improved alveolar development by reducing septal thickness, and reduced the influx of leukocytes. Analysis of mRNA expression revealed an iNO-induced downregulation of genes involved in inflammation (IL-6, cytokine-induced neutrophilic chemoattractant-1, and amphiregulin), coagulation, fibrinolysis (plasminogen activator inhibitor 1 and urokinase-type plasminogen activator receptor), cell cycle regulation (p21), and an upregulation of fibroblast growth factor receptor-4 (alveolar formation). We conclude that iNO therapy improves lung pathology and prolongs survival by reducing septum thickness, inhibiting inflammation, and reducing alveolar fibrin deposition in premature rat pups with neonatal hyperoxic lung injury. 相似文献
968.
Horst Mt Brouwer E Verwijnen S Rodijk M de Jong M Hoeben R de Leeuw B Smitt PS 《The journal of gene medicine》2007,9(12):1071-1079
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein abundantly expressed in malignant gliomas. We have constructed a novel oncolytic adenovirus, Ad5-gfa2(B)3-E1, for treatment of these tumors. In this construct, the E1 region is under control of the tissue-specific GFAP promoter (gfa2) with three additional copies of the glial specific 'B' enhancer. Infection of a GFAP-positive cell line with Ad5-gfa2(B)3-E1 resulted in E1A and E1B expression at 75% and 30% of the levels obtained after wtAd5 infection. Q-PCR showed that Ad5-gfa2(B)3-E1 replicated 4.5 times more efficiently in the GFAP-positive than in the GFAP-negative cell lines. Cell viability assays showed efficient elimination of GFAP-positive cells by Ad5-gfa2(B)3-E1, in some cell lines as efficiently as wtAd5, while the elimination was attenuated in GFAP-negative cell lines. When tested in human tumor xenografts in nude mice, Ad5-gfa2(B)3-E1 effectively suppressed the growth of GFAP-positive SNB-19 glial tumors but not of GFAP-negative A549 lung tumors. In Ad5-gfa2(B)3-E1, the E3 region was deleted to create space for future insertion of heterologous therapeutic genes. Experiments with dl7001, an E3-deleted variant of wtAd5, confirmed that the specificity of Ad5-gfa2(B)3-E1 replication was based on the promoter driving E1 and not on the E3 deletion. Strategies to further improve the efficacy of Ad5-gfa2(B)3-E1 for the treatment of malignant gliomas include the insertion of therapeutic genes in E3 or retargeting to receptors that are more abundantly expressed on primary glioma cells than CAR. 相似文献
969.
Péter Maróti 《BBA》2019,1860(4):317-324
In the native and most mutant reaction centers of bacterial photosynthesis, the electron transfer is coupled to proton transfer and is rate limiting for the second reduction of QB??→?QBH2. In the presence of divalent metal ions (e.g. Cd2+) or in some (“proton transfer”) mutants (L210DN/M17DN or L213DN), the proton delivery to QB? is made rate limiting and the properties of the proton pathway can be directly examined. We found that small weak acids and buffers in large concentrations (up to 1?M) were able to rescue the severely impaired proton transfer capability differently depending on the location of the defects: lesions at the protein surface (proton gate H126H/H128H?+?Cd2+), beneath the surface (M17DN?+?Cd2+, L210DN/M17DN) or deep inside the protein (L213DN) could be completely, partially or to very small extent recovered, respectively. Small zwitterionic acids (azide/hydrazoic acid) and buffers (tricine) proved to be highly effective rescuers consistent with their enhanced binding affinity and access to any of the proton acceptors (including QB? itself) in the pathway. As a consequence, back titration of the protons at L212Glu could be observed as a pH-dependence of the rate constant of the charge recombination in the presence of azide or formate. Model calculations support the collective influence of the acid cluster on the change of the protonation states upon extension of the cluster with the bound small acid. In proton transfer mutants, the rescuing agents decreased the free energy of activation together with their enthalpic and entropic components. This is in agreement with the hypothesis that they function as protein-penetrating protonophores delivering protons into the chain and select dominating paths out of many alternate routes. We estimate that the proton delivery will be accelerated in one pathway out of 100–200 alternate pathways. The implications for design of the chemical recovery of impaired intra-protein proton transfer pathways in proton transfer mutants are discussed. 相似文献
970.
Kovács Anita K. Hegyes Péter Szebeni Gábor J. Bogár Krisztián Puskás László G. Tóth Gábor K. 《International journal of peptide research and therapeutics》2019,25(3):1209-1215
International Journal of Peptide Research and Therapeutics - The synthesis of peptide-luciferin conjugates has a pivotal role in the development of bioluminescent detection systems that are based... 相似文献