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81.
Background
Pancreatic-tail duct ligation (PDL) in adult rodents has been reported to induce beta cell generation and increase beta cell mass but increases in beta cell number have not been demonstrated. This study examines whether PDL increases beta cell number and whether this is caused by neogenesis of small clusters and/or their growth to larger aggregates.Methodology
Total beta cell number and its distribution over small (<50 µm), medium, large (>100 µm) clusters was determined in pancreatic tails of 10-week-old mice, 2 weeks after PDL or sham.Principal findings
PDL increased total beta cell mass but not total beta cell number. It induced neogenesis of small beta cell clusters (2.2-fold higher number) which contained a higher percent proliferating beta cells (1.9% Ki67+cells) than sham tails (<0.2%); their higher beta cell number represented <5% of total beta cell number and was associated with a similar increase in alpha cell number. It is unknown whether the regenerative process is causally related to the inflammatory infiltration in PDL-tails. Human pancreases with inflammatory infiltration also exhibited activation of proliferation in small beta cell clusters.Conclusions/significance
The PDL model illustrates the advantage of direct beta cell counts over beta cell mass measurements when assessing and localizing beta cell regeneration in the pancreas. It demonstrates the ability of the adult mouse pancreas for neogenesis of small beta cell clusters with activated beta cell proliferation. Further studies should investigate conditions under which neoformed small beta cell clusters grow to larger aggregates and hence to higher total beta cell numbers. 相似文献82.
83.
Penelope Koraka Byron E. E. Martina Jouke M. Roose Pieter-Paul A. M. van Thiel Geert van Amerongen Thijs Kuiken Albert D. M. E. Osterhaus 《PLoS pathogens》2012,8(5)
A fatal human case of Duvenhage virus (DUVV) infection in a Dutch traveller who had returned from Kenya was reported in 2007. She exhibited classical symptoms of rabies encephalitis with distinct pathological findings. In the present study we describe the isolation and characterization of DUVV in vitro and its passage in BALB/c mice. The virus proved to be neuroinvasive in both juvenile and adult mice, resulting in about 50% lethality upon peripheral infection. Clinical signs in infected mice were those of classical rabies. However, the distribution of viral antigen expression in the brain differed from that of classical rabies virus infection and neither inclusion bodies nor neuronal necrosis were observed. This is the first study to describe the in vitro and in vivo isolation and characterization of DUVV. 相似文献
84.
Jelluma N Brenkman AB van den Broek NJ Cruijsen CW van Osch MH Lens SM Medema RH Kops GJ 《Cell》2008,132(2):233-246
Maintenance of chromosomal stability relies on coordination between various processes that are critical for proper chromosome segregation in mitosis. Here we show that monopolar spindle 1 (Mps1) kinase, which is essential for the mitotic checkpoint, also controls correction of improper chromosome attachments. We report that Borealin/DasraB, a member of the complex that regulates the Aurora B kinase, is directly phosphorylated by Mps1 on residues that are crucial for Aurora B activity and chromosome alignment. As a result, cells lacking Mps1 kinase activity fail to efficiently align chromosomes due to impaired Aurora B function at centromeres, leaving improper attachments uncorrected. Strikingly, Borealin/DasraB bearing phosphomimetic mutations restores Aurora B activity and alignment in Mps1-depleted cells. Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments. 相似文献
85.
Vankerckhoven V Huys G Vancanneyt M Snauwaert C Swings J Klare I Witte W Van Autgaerden T Chapelle S Lammens C Goossens H 《Applied and environmental microbiology》2008,74(14):4247-4255
The intraspecific relationships among a collection of Enterococcus faecium isolates comprising probiotic cultures and human clinical isolates were investigated through the combined use of two high-resolution DNA-fingerprinting techniques. In addition, the incidences of antimicrobial resistance and virulence traits were investigated. A total of 128 E. faecium isolates from human clinical or nonclinical sources or used as probiotic cultures were subjected to fluorescent amplified fragment length polymorphism (FAFLP) fingerprinting and pulsed-field gel electrophoresis (PFGE) analysis of SmaI macrorestriction patterns. Susceptibilities to 16 antimicrobial agents were tested using broth microdilution, and the presence of the corresponding resistance genes was investigated using PCR. Multiplex PCR was used to detect the presence of the enterococcal virulence genes asa1, gelE, cylA, esp, and hyl. The results of the study showed that two intraspecific genomic groups (I and II) were obtained in FAFLP analysis. PFGE analysis demonstrated high variability within these two groups but also indicated that some probiotic cultures were indistinguishable and that a number of clinical isolates may be reisolations of commercial probiotic cultures. Compared to group II, which contained the majority of the probiotic isolates and fewer human clinical isolates, higher phenotypic and genotypic resistance frequencies were observed in group I. Two probiotic isolates were phenotypically resistant to erythromycin, one of which contained an erm(B) gene that was not transferable to enterococcal recipients. None of the probiotic E. faecium isolates demonstrated the presence of the tested virulence genes. The previously reported observation that E. faecium consists of two intraspecific genomic groups was further substantiated by FAFLP fingerprinting of 128 isolates. In combination with antimicrobial resistance and virulence testing, this grouping might represent an additional criterion in assessing the safety of new potential probiotic E. faecium isolates. 相似文献
86.
van Dam EA Dams SD Peters GW Rutten MC Schurink GW Buth J van de Vosse FN 《Biomechanics and modeling in mechanobiology》2008,7(2):127-137
The objective of this work was to determine the linear and non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus
and to study the changes in mechanical properties throughout the thickness of the thrombus. Samples are gathered from thrombi
of seven patients. Linear viscoelastic data from oscillatory shear experiments show that the change of properties throughout
the thrombus is different for each thrombus. Furthermore the variations found within one thrombus are of the same order of
magnitude as the variation between patients. To study the non-linear regime, stress relaxation experiments are performed.
To describe the phenomena observed experimentally, a non-linear multimode model is presented. The parameters for this model
are obtained by fitting this model successfully to the experiments. The model cannot only describe the average stress response
for all thrombus samples but also the highest and lowest stress responses. To determine the influence on the wall stress of
the behavior observed the model proposed needs to implemented in the finite element wall stress analysis. 相似文献
87.
Leen Verbert Bora Lee Sarah L Kocks Zerihun Assefa Jan B Parys Ludwig Missiaen Geert Callewaert Rafael A Fissore Humbert De Smedt Geert Bultynck 《Biology of the cell / under the auspices of the European Cell Biology Organization》2008,100(1):39-49
BACKGROUND INFORMATION: The IP(3)R (inositol 1,4,5-trisphosphate receptor) is a tetrameric channel that accounts for a large part of the intracellular Ca(2+) release in virtually all cell types. We have previously demonstrated that caspase-3-mediated cleavage of IP(3)R1 during cell death generates a C-terminal fragment of 95 kDa comprising the complete channel domain. Expression of this truncated IP(3)R increases the cellular sensitivity to apoptotic stimuli, and it was postulated to be a constitutively active channel. RESULTS: In the present study, we demonstrate that expression of the caspase-3-cleaved C-terminus of IP(3)R1 increased the rate of thapsigargin-mediated Ca(2+) leak and decreased the rate of Ca(2+) uptake into the ER (endoplasmic reticulum), although it was not sufficient by itself to deplete intracellular Ca(2+) stores. We detected the truncated IP(3)R1 in different cell types after a challenge with apoptotic stimuli, as well as in aged mouse oocytes. Injection of mRNA corresponding to the truncated IP(3)R1 blocked sperm factor-induced Ca(2+) oscillations and induced an apoptotic phenotype. CONCLUSIONS: In the present study, we show that caspase-3-mediated truncation of IP(3)R1 enhanced the Ca(2+) leak from the ER. We suggest a model in which, in normal conditions, the increased Ca(2+) leak is largely compensated by enhanced Ca(2+)-uptake activity, whereas in situations where the cellular metabolism is compromised, as occurring in aging oocytes, the Ca(2+) leak acts as a feed-forward mechanism to divert the cell into apoptosis. 相似文献
88.
Alain Van Muylem Pierre Alain Gevenois Elizabeth Kallinger Alexander A Bankier Christiane Knoop Geert Verleden Marc Estenne 《Journal of applied physiology》2008,104(1):224-229
After single-lung transplantation (SLT) for emphysema, heterogeneity of ventilation distribution in the graft can be assessed by measuring the slope of the alveolar plateau, computed from a single-breath test, performed in lateral decubitus with this lung in the nondependent position. We tested the validity of this technique in patients with SLT for interstitial lung diseases (ILD). Twelve patients with SLT for ILD, 12 nontransplanted patients with ILD, and 10 healthy control subjects performed single-breath washouts in right and left lateral decubitus; nitrogen slope (S(N(2))) and the difference between SF(6) and He slopes (S(SF(6))-S(He)) were measured between 75 and 100% of expired volume. In 10 transplant recipients, the volume of each lung was measured in both postures by computerized tomography. Slopes were unaffected by posture in normal control subjects and patients with ILD. On the other hand, S(N(2)) and S(SF(6))-S(He) in transplant recipients were smaller with the graft in the nondependent than in the dependent position (0.366 +/- 0.445 vs. 1.035 +/- 0.498 for S(N(2)); 0.094 +/- 0.201 vs. 0.218 +/- 0.277 for S(SF(6))-S(He)). Values of S(N(2)) and S(SF(6))-S(He) obtained in the former position were similar to those obtained in normal controls, while values obtained in the latter position were similar to those obtained in nontransplanted patients with ILD. Computerized tomography studies with the graft in the nondependent position indicated that this lung contributed 82% of the volume expired below functional residual capacity. We conclude that, in patients with SLT for ILD, the slope of the alveolar plateau obtained with the graft in the nondependent position reflects heterogeneity of ventilation distribution in this lung. 相似文献
89.
van den Bogaart G Guzmán JV Mika JT Poolman B 《The Journal of biological chemistry》2008,283(49):33854-33857
The mechanism of pore formation of lytic peptides, such as melittin from bee venom, is thought to involve binding to the membrane surface, followed by insertion at threshold levels of bound peptide. We show that in membranes composed of zwitterionic lipids, i.e. phosphatidylcholine, melittin not only forms pores but also inhibits pore formation. We propose that these two modes of action are the result of two competing reactions: direct insertion into the membrane and binding parallel to the membrane surface. The direct insertion of melittin leads to pore formation, whereas the parallel conformation is inactive and prevents other melittin molecules from inserting, hence preventing pore formation. 相似文献
90.
Speybroeck N Marcotty T Aerts M Dolan T Williams B Lauer J Molenberghs G Burzykowski T Mulumba M Berkvens D 《Experimental parasitology》2008,118(4):522-530
Theileria parva is the causative agent of East Coast fever (ECF), an important cattle disease in East and Central Africa. One of the methods for control of ECF is 'infection and treatment', a procedure in which an animal is infected with the live parasite and at the same time treated with a long-acting oxytetracycline formulation, restraining the infection and allowing a protective cellular immune response to develop. Optimal immunizing doses were estimated using models of trichotomous response: dysimmunization (death or severe reaction during immunization), immunization failure (death or severe reaction during lethal challenge) and successful immunization (neither dysimmunization nor immunization failure). In this paper we present methods of interpreting immunization trials and apply these methods to previously unpublished data from two such trials: one with a mixture of three T. parva stocks and one with a single T. parva stock. We explain why titration trials conducted with a cocktail of antigens could predict a suboptimal immunization dose. Indeed it is possible for a combination of three individually efficient stocks to result in a mixture with which optimal immunization response might be difficult to achieve, because of averaging effects. The corresponding interpretation provides insights into why standard immunization trials for T. parva have not yielded the results that might be expected of them. The results of this work may also have implications for the use of antigen cocktails in cancer, HIV and malaria vaccine trials. 相似文献