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151.
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
152.
The basidiomycete Phlebia centrifuga is a wood-decay fungus characteristic for unmanaged old-growth forests of spruce, a habitat that has become increasingly fragmented due to forest management. The aim of this study was to investigate the genetic population structures of P. centrifuga in both continuous and fragmented habitats, and estimate the potential impact of fragmentation on the genetic diversity of the fungus. Three hundred fifteen single spore isolates (representing 47 spore families and 33 single isolates) from eight populations across northern Europe (Russia, Finland, and Sweden) were screened with seven microsatellite markers and arbitrary primed polymerase chain reaction with the M13 minisatellite. The two molecular methods generally gave the same pattern for the genetic population structure. There were no significant differences between the observed and the expected heterozygosities, and the inbreeding coefficient (FIS) did not indicate any inbreeding. The fixation index (FST) revealed a general pattern with little to moderate genetic differentiation for the majority of populations, while the southernmost Swedish population Norra Kvill was the only one showing high differentiation from about half of the other populations. Swedish population Fiby with the shortest distance to the continuous habitat was moderately differentiated from most of the others and to the largest extent differed from geographically closest population of Norra Kvill. The results indicate that the fragmentation of old-growth forest in Russia and Finland is more recent than the fragmentation in Sweden, and the genetic population structures of P. centrifuga in northern Europe might be related to differences in forest landscape dynamics between the two areas. 相似文献
153.
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
154.
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
155.
Kaiser A Hammels I Gottwald A Nassar M Zaghloul MS Motaal BA Hauber J Hoerauf A 《Bioorganic & medicinal chemistry》2007,15(18):6200-6207
156.
Fusiogenic endogenous-retroviral syncytin-1 exerts anti-apoptotic functions in staurosporine-challenged CHO cells 总被引:1,自引:0,他引:1
Knerr I Schnare M Hermann K Kausler S Lehner M Vogler T Rascher W Meissner U 《Apoptosis : an international journal on programmed cell death》2007,12(1):37-43
Fusiogenic glycoprotein syncytin-1, expressed in human placenta, is a promising candidate for acquiring a basic knowledge
of placental syncytialization. However, its cellular mode of action is unidentified. We investigated whether syncytin-1 may
exert influence on apoptotic processes. Therefore, we incubated CHO cells after stable transfection with syncytin-1 (CHO-52)
in the presence or absence of staurosporine (STS), a kinase inhibitor well characterized to induce apoptosis. When testing
the phenotype of CHO-52 cells, we could demonstrate that the induction of apoptosis by STS was delayed over a period of up
to 24 h. Furthermore, the cell death rate was decreased by approx 75% following transfection of syncytin-1 in CHO-52 compared
to mock-treated cells. In detail, after 18h of incubation with 500 nM STS, 64 ± 2% of CHO-52 cells were viable compared to
16 ± 1% of CHO-mocks, after 24 h 43 ± 3% vs 5 ± 2%, respectively. CHO-52 cells exhibited a lower expression of active caspase
3 and anti-apoptotic Bcl-2 was found to be increased in CHO-52 cells at baseline and following STS treatment.
Our study provides first evidence that syncytin-1 serves anti-apoptotic function under certain conditions. A lessened activation
of caspase 3 and an increased expression of Bcl-2 are possible mechanisms. 相似文献
157.
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
158.
Novel blocker of NFAT activation inhibits IL-6 production in human myometrial arteries and reduces vascular smooth muscle cell proliferation 总被引:1,自引:0,他引:1
159.
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
160.
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