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91.
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93.
Stimac G Dimanovski J Trnski D Katusić J Ruzić B Spajić B Reljić A Padovan M Kraus O 《Collegium antropologicum》2007,31(4):1055-1060
We demonstrate the evolution of the clinical presentation and outcomes for patients with clinically localized prostate cancer (PC) treated with radical retropubic prostatectomy (RRP) at our department, emphasizing epidemiologic significance of changes during the 10-year period. We assessed the annual trends for changes in patients age, preoperative prostate specific antigen (PSA), preoperative versus postoperative stages and Gleason grades, organ confined status and surgical margin status. A total of 488 RRPs were performed from January 1996 to December 2005 with the annual frequency increased from 8 to 129 (1512.5%). Mean patient age increased from 61.5 to 66.12 years in 2005, with the percentage of men aged more than 70 years increased from 12.5 to 26.5%, respectively. The detection of PC based solely on pathological PSA levels (as indication for prostate biopsy) rose impressively from 25.5 to 70% and the rates of postoperative organ-confined disease also increased significantly from 25 to 74.7%. Mean preoperative PSA decreased from 16.7 to 9.89 ng/mL. On the contrary, there was an increase in percentage of patients with preoperative PSA values ranging from 4 to 10 ng/mL (from 20 to 65.4%). Positive surgical margin rate decreased from 49.4 to 25% and percent of patients receiving neoadjuvant therapy decreased from 78.5 to 5.4%. Proportion of patients who were undergraded decreased from 75.1 to 31.7%. The rates of understaging have remained relatively stable over the years. During the study period, PC was increasingly detected by prostate biopsy on the basis of a pathological PSA level only and shifted significantly to more organ-confined stages with more favourable outcomes for pathological variables due to a more accurate assessment of clinical stage prior to surgery, reduced use of neoadjuvant therapy and improved surgical technique. Our data also argue strongly that routine PSA testing should be expanded and not restricted. 相似文献
94.
Tasler S Kraus J Wuzik A Müller O Aschenbrenner A Cubero E Pascual R Quintana-Ruiz JR Dordal A Mercè R Codony X 《Bioorganic & medicinal chemistry letters》2007,17(22):6224-6229
Based on a pharmacophore alignment on a 5-HT(6) ligand applying 4SCan technology, a new lead series was identified and further structurally investigated. K(i)s down to 8 nM were achieved. 相似文献
95.
Frasier TR Hamilton PK Brown MW Conger LA Knowlton AR Marx MK Slay CK Kraus SD White BN 《Molecular ecology》2007,16(24):5277-5293
Parentage analyses of baleen whales are rare, and although mating systems have been hypothesized for some species, little data on realized male reproductive success are available and the patterns of male reproductive success have remained elusive for most species. Here we combine over 20 years of photo-identification data with high-resolution genetic data for the majority of individual North Atlantic right whales to assess paternity in this endangered species. There was significant skew in male reproductive success compared to what would be expected if mating was random (P < 0.001). The difference was due to an excess of males assigned zero paternities, a deficiency of males assigned one paternity, and an excess of males assigned as fathers for multiple calves. The variance in male reproductive success was high relative to other aquatically mating marine mammals, but was low relative to mammals where the mating system is based on resource- and/or mate-defence polygyny. These results are consistent with previous data suggesting that the right whale mating system represents one of the most intense examples of sperm competition in mammals, but that sperm competition on its own does not allow for the same degree of polygyny as systems where males can control access to resources and/or mates. The age distribution of assigned fathers was significantly biased towards older males (P < 0.05), with males not obtaining their first paternity until approximately 15 years of age, which is almost twice the average age of first fertilization in females (8 years), suggesting that mate competition is preventing younger males from reproducing. The uneven distribution of paternities results in a lower effective population size in this species that already has one of the lowest reported levels of genetic diversity, which may further inhibit reproductive success through mate incompatibility of genetically similar individuals. 相似文献
96.
Piddubnyak V Rigou P Michel L Rain JC Geneste O Wolkenstein P Vidaud D Hickman JA Mauviel A Poyet JL 《Cell death and differentiation》2007,14(6):1222-1233
As a component of the apoptosome, a caspase-activating complex, Apaf-1 plays a central role in the mitochondrial caspase activation pathway of apoptosis. We report here the identification of a novel Apaf-1 interacting protein, hepatocellular carcinoma antigen 66 (HCA66) that is able to modulate selectively Apaf-1-dependent apoptosis through its direct association with the CED4 domain of Apaf-1. Expression of HCA66 was able to potentiate Apaf-1, but not receptor-mediated apoptosis, by increasing downstream caspase activity following cytochrome c release from the mitochondria. Conversely, cells depleted of HCA66 were severely impaired for apoptosome-dependent apoptosis. Interestingly, expression of the Apaf-1-interacting domain of HCA66 had the opposite effect of the full-length protein, interfering with the Apaf-1 apoptotic pathway. Using a cell-free system, we showed that reduction of HCA66 expression was associated with a diminished amount of caspase-9 in the apoptosome, resulting in a lower ability of the apoptosome to activate caspase-3. HCA66 maps to chromosome 17q11.2 and is among the genes heterozygously deleted in neurofibromatosis type 1 (NF1) microdeletion syndrome patients. These patients often have a distinct phenotype compared to other NF1 patients, including a more severe tumour burden. Our results suggest that reduced expression of HCA66, owing to haploinsufficiency of HCA66 gene, could render NF1 microdeleted patients-derived cells less susceptible to apoptosis. 相似文献
97.
Koenitzer JR Isbell TS Patel HD Benavides GA Dickinson DA Patel RP Darley-Usmar VM Lancaster JR Doeller JE Kraus DW 《American journal of physiology. Heart and circulatory physiology》2007,292(4):H1953-H1960
Hydrogen sulfide (H(2)S) has recently been shown to have a signaling role in vascular cells. Similar to nitric oxide (NO), H(2)S is enzymatically produced by amino acid metabolism and can cause posttranslational modification of proteins, particularly at thiol residues. Molecular targets for H(2)S include ATP-sensitive K(+) channels, and H(2)S may interact with NO and heme proteins such as cyclooxygenase. It is well known that the reactions of NO in the vasculature are O(2) dependent, but this has not been addressed in most studies designed to elucidate the role of H(2)S in vascular function. This is important, since H(2)S reactions can be dramatically altered by the high concentrations of O(2) used in cell culture and organ bath experiments. To test the hypothesis that the effects of H(2)S on the vasculature are O(2) dependent, we have measured real-time levels of H(2)S and O(2) in respirometry and vessel tension experiments, as well as the associated vascular responses. A novel polarographic H(2)S sensor developed in our laboratory was used to measure H(2)S levels. Here we report that, in rat aorta, H(2)S concentrations that mediate rapid contraction at high O(2) levels cause rapid relaxation at lower physiological O(2) levels. At high O(2), the vasoconstrictive effect of H(2)S suggests that it may not be H(2)S per se but, rather, a putative vasoactive oxidation product that mediates constriction. These data are interpreted in terms of the potential for H(2)S to modulate vascular tone in vivo. 相似文献
98.
Large-conductance calcium-activated potassium channel activity is absent in human and mouse neutrophils and is not required for innate immunity 总被引:2,自引:0,他引:2
Essin K Salanova B Kettritz R Sausbier M Luft FC Kraus D Bohn E Autenrieth IB Peschel A Ruth P Gollasch M 《American journal of physiology. Cell physiology》2007,293(1):C45-C54
Large-conductance Ca2+-activated K+ (BK) channels are reported to be essential for NADPH oxidase-dependent microbial killing and innate immunity in leukocytes. Using human peripheral blood and mouse bone marrow neutrophils, pharmacological targeting, and BK channel gene-deficient (BK/) mice, we stimulated NADPH oxidase activity with 12-O-tetradecanoylphorbol-13-acetate (PMA) and performed patch-clamp recordings on isolated neutrophils. Although PMA stimulated NADPH oxidase activity as assessed by O2 and H2O2 production, our patch-clamp experiments failed to show PMA-activated BK channel currents in neutrophils. In our studies, PMA induced slowly activating currents, which were insensitive to the BK channel inhibitor iberiotoxin. Instead, the currents were blocked by Zn2+, which indicates activation of proton channel currents. BK channels are gated by elevated intracellular Ca2+ and membrane depolarization. We did not observe BK channel currents, even during extreme depolarization to +140 mV and after elevation of intracellular Ca2+ by N-formyl-L-methionyl-L-leucyl-phenylalanine. As a control, we examined BK channel currents in cerebral and tibial artery smooth muscle cells, which showed characteristic BK channel current pharmacology. Iberiotoxin did not block killing of Staphylococcus aureus or Candida albicans. Moreover, we addressed the role of BK channels in a systemic S. aureus and Yersinia enterocolitica mouse infection model. After 3 and 5 days of infection, we found no differences in the number of bacteria in spleen and kidney between BK/ and BK+/+ mice. In conclusion, our experiments failed to identify functional BK channels in neutrophils. We therefore conclude that BK channels are not essential for innate immunity. killing assay; reactive oxygen species; BK-deficient mice; mice infection 相似文献
99.
O. Horner J-M. Mouesca P. L. Solari M. Orio J-L. Oddou P. Bonville H. M. Jouve 《Journal of biological inorganic chemistry》2007,12(4):509-525
The catalase from Proteus mirabilis peroxide-resistant bacteria is one of the most efficient heme-containing catalases. It forms a relatively stable compound II. We were able to prepare samples of compound II from P. mirabilis catalase enriched in 57Fe and to study them by spectroscopic methods. Two different forms of compound II, namely, low-pH compound II (LpH II) and high-pH compound II (HpH II), have been characterized by Mössbauer, extended X-ray absorption fine structure (EXAFS) and UV-vis absorption spectroscopies. The proportions of the two forms are pH-dependent and the pH conversion between HpH II and LpH II is irreversible. Considering (1) the Mössbauer parameters evaluated for four related models by density functional theory methods, (2) the existence of two different Fe–Oferryl bond lengths (1.80 and 1.66 Å) compatible with our EXAFS data and (3) the pH dependence of the α band to β band intensity ratio in the absorption spectra, we attribute the LpH II compound to a protonated ferryl FeIV–OH complex (Fe–O approximately 1.80 Å), whereas the HpH II compound corresponds to the classic ferryl FeIV=O complex (Fe=O approximately 1.66 Å). The large quadrupole splitting value of LpH II (measured 2.29 mm s?1 vs. computed 2.15 mm s?1) compared with that of HpH II (measured 1.47 mm s?1 vs. computed 1.46 mm s?1) reflects the protonation of the ferryl group. The relevancy and involvement of such (FeIV=O/FeIV–OH) species in the reactivity of catalase, peroxidase and chloroperoxidase are discussed. 相似文献
100.
Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities
in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs, especially naproxen,
is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis
(JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases. In
addition, we prospectively studied the incidence of PP in 196 patients (127 girls and 69 boys) with JIA and associated diseases
treated with naproxen from July 2001 to March 2002. We compared these data with those from a matched control group with JIA
and associated diseases not treated with naproxen in order to identify risk factors for development of PP. The incidence of
PP in the group of children taking naproxen was 11.4%. PP was particularly frequent in children with the early-onset pauciarticular
subtype of JIA (mean age 4.5 years). PP was associated with signs of disease activity, such as reduced haemoglobin (<11.75
g/dl), and increased leucocyte counts (>10,400/μl) and erythocyte sedimentation rate (>26 mm/hour). Comedications, especially
chloroquine intake, appeared to be additional risk factors. The mean duration of naproxen therapy before the onset of PP was
18.1 months, and most children with PP developed their lesions within the first 2 years of naproxen treatment. JIA disease
activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who
have significant inflammation appear to be prone to developing PP upon treatment with naproxen. 相似文献