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991.
Granell S Baldini G Mohammad S Nicolin V Narducci P Storrie B Baldini G 《Molecular biology of the cell》2008,19(2):572-586
A variant alpha1-antitrypsin with E342K mutation has a high tendency to form intracellular polymers, and it is associated with liver disease. In the hepatocytes of individuals carrying the mutation, alpha1-antitrypsin localizes both to the endoplasmic reticulum (ER) and to membrane-surrounded inclusion bodies (IBs). It is unclear whether the IBs contribute to cell toxicity or whether they are protective to the cell. We found that in hepatoma cells, mutated alpha1-antitrypsin exited the ER and accumulated in IBs that were negative for autophagosomal and lysosomal markers, and contained several ER components, but not calnexin. Mutated alpha1-antitrypsin induced IBs also in neuroendocrine cells, showing that formation of these organelles is not cell type specific. In the presence of IBs, ER function was largely maintained. Increased levels of calnexin, but not of protein disulfide isomerase, inhibited formation of IBs and lead to retention of mutated alpha1-antitrypsin in the ER. In hepatoma cells, shift of mutated alpha1-antitrypsin localization to the ER by calnexin overexpression lead to cell shrinkage, ER stress, and impairment of the secretory pathway at the ER level. We conclude that segregation of mutated alpha1-antitrypsin from the ER to the IBs is a protective cell response to maintain a functional secretory pathway. 相似文献
992.
Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat 总被引:1,自引:0,他引:1
Accorsi-Mendonça T Paiva KB Zambuzzi WF Cestari TM Lara VS Sogayar MC Taga R Granjeiro JM 《Journal of molecular histology》2008,39(2):201-208
MMPs are endopeptidases that play a pivotal role in ECM turnover. RECK is a single membrane-anchored MMP-regulator. Here,
we evaluated the temporal and spatial expression of MMP-2, MMP-9, and RECK during alveolar bone regeneration. The maxillary
central incisor of Wistar rats was extracted and the animals were killed at 1, 3, 7, 10, 14, 21, 28, and 42 days post-operatively
(n = 3/period). The hemimaxillae were collected, demineralized and embedded in paraffin. Immunohistochemical analysis was performed
by the immunoperoxidase technique with polyclonal antibodies. On day 1, polymorphonuclear cells in the blood clot presented
mild immunolabeling for MMPs. During bone remodeling, osteoblasts facing new bone showed positive staining for gelatinases
and RECK in all experimental periods. MMPs were also found in the connective tissue and endothelial cells. Our results show
for the first time that inactive and/or active forms of MMP-2, MMP-9 and RECK are differentially expressed by osteogenic and
connective cells during several events of alveolar bone regeneration. This may be important for the replacement of the blood
clot by connective tissue, and in the formation, maturation and remodeling of new bone. 相似文献
993.
Chytridiomycosis and Amphibian Population Declines Continue to Spread Eastward in Panama 总被引:1,自引:0,他引:1
Woodhams DC Kilburn VL Reinert LK Voyles J Medina D Ibáñez R Hyatt AD Boyle DG Pask JD Green DM Rollins-Smith LA 《EcoHealth》2008,5(3):268-274
Chytridiomycosis is a globally emerging disease of amphibians and the leading cause of population declines and extirpations
at species-diverse montane sites in Central America. We continued long-term monitoring efforts for the presence of the fungal
pathogen Batrachochytrium dendrobatidis (Bd) and for amphibian populations at two sites in western Panama, and we began monitoring at three new sites to the east. Population
declines associated with chytridiomycosis emergence were detected at Altos de Campana National Park. We also detected Bd in three species east of the Panama Canal at Soberanía National Park, and prevalence data suggests that Bd may be enzootic in the lowlands of the park. However, no infected frogs were found further east at Tortí (prevalence <7.5%
with 95% confidence). Our results suggest that Panama’s diverse and not fully described amphibian communities east of the
canal are at risk. Precise predictions of future disease emergence events are not possible until factors underlying disease
emergence, such as dispersal, are understood. However, if the fungal pathogen spreads in a pattern consistent with previous
disease events in Panama, then detection of Bd at Tortí and other areas east of the Panama Canal is imminent. Therefore, development of new management strategies and increased
precautions for tourism, recreation, and biology are urgently needed. 相似文献
994.
Xunbin Wei Vanessa G. Henke Carsten Strübing Edward B. Brown David E. Clapham 《Biophysical journal》2003,84(2):1317-1327
The NPC is the portal for the exchange of proteins, mRNA, and ions between nucleus and cytoplasm. Many small molecules (<10 kDa) permeate the nucleus by simple diffusion through the pore, but molecules larger than 70 kDa require ATP and a nuclear localization sequence for their transport. In isolated Xenopus oocyte nuclei, diffusion of intermediate-sized molecules appears to be regulated by the NPC, dependent upon [Ca2+] in the nuclear envelope. We have applied real-time imaging and fluorescence recovery after photobleaching to examine the nuclear pore permeability of 27-kDa EGFP in single intact cells. We found that EGFP diffused bidirectionally via the NPC across the nuclear envelope. Although diffusion is slowed ~100-fold at the nuclear envelope boundary compared to diffusion within the nucleus or cytoplasm, this delay is expected for the reduced cross-sectional area of the NPCs. We found no evidence for significant nuclear pore gating or block of EGFP diffusion by depletion of perinuclear Ca2+ stores, as assayed by a nuclear cisterna-targeted Ca2+ indicator. We also found that EGFP exchange was not altered significantly during the cell cycle. 相似文献
995.
996.
Selective Defecation and Selective Foraging: Antiparasite Behavior in Wild Ungulates? 总被引:4,自引:0,他引:4
Vanessa O. Ezenwa 《Ethology : formerly Zeitschrift fur Tierpsychologie》2004,110(11):851-862
Selective defecation and selective foraging are two potential antiparasite behaviors used by grazing ungulates to reduce infection by fecal–oral transmitted parasites. While there is some evidence that domestic species use these strategies, less is known about the occurrence and efficacy of these behaviors in wild ungulates. In this study, I examined whether wild antelope use selective defecation and selective foraging strategies to reduce exposure to gastrointestinal nematode parasites. By quantifying parasite levels in the environment in relation to the defecation patterns of three species, dik‐dik (Madoqua kirkii), Grant's gazelle (Gazella granti), and impala (Aepyceros melampus), I found that nematode larval concentrations in pasture were higher in the vicinity of clusters of feces (dung middens) compared to single fecal pellet groups or dung‐free areas. In addition, experimental feeding trials in free‐ranging dik‐dik showed that individuals selectively avoided feeding near concentrations of feces. Given that increased parasite contamination was found in the immediate vicinity of fecal clusters, fecal avoidance could help reduce host consumption of parasites and may therefore be an effective antiparasite behavior for certain species. On the other hand, while the concentration of parasite larvae in the vicinity of middens coupled with host avoidance of these areas during grazing could reduce host contact with parasites, results showing a positive correlation between the number of middens in a habitat and larval abundance at control sites suggest that dung middens might increase and not decrease overall host exposure to parasites. If this is the case, dung midden formation may not be a viable antiparasite strategy. 相似文献
997.
Evaluation of the Biological Sampling Kit (BiSKit) for Large-Area Surface Sampling 总被引:5,自引:5,他引:0 下载免费PDF全文
Mark P. Buttner Patricia Cruz Linda D. Stetzenbach Amy K. Klima-Comba Vanessa L. Stevens Peter A. Emanuel 《Applied microbiology》2004,70(12):7040-7045
Current surface sampling methods for microbial contaminants are designed to sample small areas and utilize culture analysis. The total number of microbes recovered is low because a small area is sampled, making detection of a potential pathogen more difficult. Furthermore, sampling of small areas requires a greater number of samples to be collected, which delays the reporting of results, taxes laboratory resources and staffing, and increases analysis costs. A new biological surface sampling method, the Biological Sampling Kit (BiSKit), designed to sample large areas and to be compatible with testing with a variety of technologies, including PCR and immunoassay, was evaluated and compared to other surface sampling strategies. In experimental room trials, wood laminate and metal surfaces were contaminated by aerosolization of Bacillus atrophaeus spores, a simulant for Bacillus anthracis, into the room, followed by settling of the spores onto the test surfaces. The surfaces were sampled with the BiSKit, a cotton-based swab, and a foam-based swab. Samples were analyzed by culturing, quantitative PCR, and immunological assays. The results showed that the large surface area (1 m2) sampled with the BiSKit resulted in concentrations of B. atrophaeus in samples that were up to 10-fold higher than the concentrations obtained with the other methods tested. A comparison of wet and dry sampling with the BiSKit indicated that dry sampling was more efficient (efficiency, 18.4%) than wet sampling (efficiency, 11.3%). The sensitivities of detection of B. atrophaeus on metal surfaces were 42 ± 5.8 CFU/m2 for wet sampling and 100.5 ± 10.2 CFU/m2 for dry sampling. These results demonstrate that the use of a sampling device capable of sampling larger areas results in higher sensitivity than that obtained with currently available methods and has the advantage of sampling larger areas, thus requiring collection of fewer samples per site. 相似文献
998.
Guillon J Moreau S Mouray E Sinou V Forfar I Fabre SB Desplat V Millet P Parzy D Jarry C Grellier P 《Bioorganic & medicinal chemistry》2008,16(20):9133-9144
Following our search for antimalarial compounds, novel series of ferrocenic pyrrolo[1,2-a]quinoxaline derivatives 1-2 were synthesized from various substituted nitroanilines and tested for in vitro activity upon the erythrocytic development of Plasmodiumfalciparum strains with different chloroquine-resistance status. The pyrrolo[1,2-a]quinoxalines 1 were prepared in 6-8 steps through a regioselective palladium-catalyzed monoamination by coupling 4-chloropyrrolo[1,2-a]quinoxalines with 1,3-bis(aminopropyl)piperazine or -methylamine using Xantphos as the ligand. The ferrocenic bispyrrolo[1,2-a]quinoxalines 2 were prepared by reductive amination of previously described bispyrrolo[1,2-a]quinoxalines 9 with ferrocene-carboxaldehyde, by treatment with NaHB(OAc)(3). The best results were observed with ferrocenic pyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus and no substitution on the terminal N-ferrocenylmethylamine function enhanced the pharmacological activity. Selected compounds 1b, 1f-h, 1l and 2a were tested for their ability to inhibit beta-haematin formation, the synthetic equivalent of hemozoin, by using the HPIA (heme polymerization inhibitory activity) assay. Of the tested compounds, only 2a showed a beta-haematin formation inhibition, but no inhibition of haem polymerization was observed with the other selected ferrocenic monopyrrolo[1,2-a]quinoxaline derivatives 1b, 1f-h and 1l, as the IC(50) values were superior to 10 equivalents. 相似文献
999.
Letícia N. Gama-de-Souza Elaine Cyreno-Oliveira Vanessa M. Freitas Edielle S. Melo Vanessa F. Vilas-Boas Anselmo S. Moriscot Ruy G. Jaeger 《Matrix biology》2008,27(5):402-419
We studied the induction of protease activity by the laminin alpha1-derived peptide AG73 in cells from adenoid cystic carcinoma (CAC2) and myoepithelioma (M1), respectively a malignant and a benign salivary gland tumors. Laminin alpha1 chain and MMP9 were immunolocalized in adenoid cystic carcinoma and myoepithelioma in vivo and in vitro. Cells grown inside AG73-enriched laminin-111 exhibited large spaces in the extracellular matrix, suggestive of remodeling. The broad spectrum MMP inhibitor GM6001 decreased spaces induced by AG73 in CAC2 and M1 cells. This result strongly suggests that AG73-mediated matrix remodeling involves matrix metalloproteinases. CAC2 and M1 cells cultured on AG73 showed a dose-dependent increase of MMP9 secretion, as detected by zymography. Furthermore, siRNA silencing of MMP9 decreased remodeling in 3D cultures. We searched for AG73 receptors regulating MMP9 activity in our cell lines. CAC2 and M1 cells grown on AG73 exhibited colocalization of syndecan-1 and beta1 integrin. siRNA knockdown of syndecan-1 expression in these cells resulted in decreased adhesion to AG73 and reduced protease and remodeling activity. We investigated syndecan-1 co-receptors in both cell lines. Silencing beta1 integrin inhibited adhesion to AG73, matrix remodeling and protease activity. Double-knockdown experiments were carried out to further explore syndecan-1 and beta1 integrin cooperation. CAC2 cells transfected with both syndecan-1 and beta1 integrin siRNA oligos showed significant decrease in adhesion to AG73. Simultaneous silencing of receptors also induced a decrease in protease activity. Our results suggest that syndecan-1 and beta1 integrin signaling downstream of AG73 regulate adhesion and MMP production by CAC2 and M1 cells. 相似文献
1000.
Jill M Ellis Hooi Kuan Tan Ruth E Gilbert David P R Muller William Henley Robert Moy Rachel Pumphrey Cornelius Ani Sarah Davies Vanessa Edwards Heather Green Alison Salt Stuart Logan 《BMJ (Clinical research ed.)》2008,336(7644):594-597
Objectives To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down’s syndrome.Design Randomised controlled trial with two by two factorial design.Setting Children living in the Midlands, Greater London, and the south west of England.Participants 156 infants aged under 7 months with trisomy 21.Intervention Daily oral supplementation with antioxidants (selenium 10 μg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo.Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months.Results Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval −2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, −1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results.Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down’s syndrome.Trial registration Clinical trials . NCT00378456相似文献