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901.
RP Finger DG Kupitz E Fenwick B Balasubramaniam RV Ramani FG Holz CE Gilbert 《PloS one》2012,7(8):e44268
Background
To explore the hypothesis that sight restoring cataract surgery provided to impoverished rural communities will improve not only visual acuity and vision-related quality of life (VRQoL) but also poverty and social status.Methods
Participants were recruited at outreach camps in Tamil Nadu, South India, and underwent free routine manual small incision cataract surgery (SICS) with intra-ocular lens (IOL) implantation, and were followed up one year later. Poverty was measured as monthly household income, being engaged in income generating activities and number of working household members. Social status was measured as rates of re-marriage amongst widowed participants. VRQoL was measured using the IND-VFQ-33. Associations were explored using logistic regression (SPSS 19).Results
Of the 294 participants, mean age ± standard deviation (SD) 60±8 years, 54% men, only 11% remained vision impaired at follow up (67% at baseline; p<0.001). At one year, more participants were engaged in income generating activities (44.7% to 77.7%; p<0.001) and the proportion of households with a monthly income <1000 Rps. decreased from 50.5% to 20.5% (p<0.05). Overall VRQoL improved (p<0.001). Participants who had successful cataract surgery were less likely to remain in the lower categories of monthly household income (OR 0.05–0.22; p<0.02) and more likely to be engaged in income earning activities one year after surgery (OR 3.28; p = 0.006). Participants widowed at baseline who had successful cataract surgery were less likely to remain widowed at one year (OR 0.02; p = 0.008).Conclusion
These findings indicate the broad positive impact of sight restoring cataract surgery on the recipients’ as well as their families’ lives. Providing free high quality cataract surgery to marginalized rural communities will not only alleviate avoidable blindness but also - to some extent - poverty in the long run. 相似文献902.
Sabina Dongol Corinne N. Thompson Simon Clare Tran Vu Thieu Nga Pham Thanh Duy Abhilasha Karkey Amit Arjyal Samir Koirala Nely Shrestha Khatri Pukar Maskey Sanjay Poudel Vijay Kumar Jaiswal Sujan Vaidya Gordon Dougan Jeremy J. Farrar Christiane Dolecek Buddha Basnyat Stephen Baker 《PloS one》2012,7(10)
Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination. 相似文献
903.
A comparison of urinary mercury between children with autism spectrum disorders and control children
Wright B Pearce H Allgar V Miles J Whitton C Leon I Jardine J McCaffrey N Smith R Holbrook I Lewis J Goodall D Alderson-Day B 《PloS one》2012,7(2):e29547
Background
Urinary mercury concentrations are used in research exploring mercury exposure. Some theorists have proposed that autism is caused by mercury toxicity. We set out to test whether mercury concentrations in the urine of children with autism were significantly increased or decreased compared to controls or siblings.Methods
Blinded cohort analyses were carried out on the urine of 56 children with autism spectrum disorders (ASD) compared to their siblings (n = 42) and a control sample of children without ASD in mainstream (n = 121) and special schools (n = 34).Results
There were no statistically significant differences in creatinine levels, in uncorrected urinary mercury levels or in levels of mercury corrected for creatinine, whether or not the analysis is controlled for age, gender and amalgam fillings.Conclusions
This study lends no support for the hypothesis of differences in urinary mercury excretion in children with autism compared to other groups. Some of the results, however, do suggest further research in the area may be warranted to replicate this in a larger group and with clear measurement of potential confounding factors. 相似文献904.
Angrisano F Riglar DT Sturm A Volz JC Delves MJ Zuccala ES Turnbull L Dekiwadia C Olshina MA Marapana DS Wong W Mollard V Bradin CH Tonkin CJ Gunning PW Ralph SA Whitchurch CB Sinden RE Cowman AF McFadden GI Baum J 《PloS one》2012,7(2):e32188
Actin dynamics have been implicated in a variety of developmental processes during the malaria parasite lifecycle. Parasite motility, in particular, is thought to critically depend on an actomyosin motor located in the outer pellicle of the parasite cell. Efforts to understand the diverse roles actin plays have, however, been hampered by an inability to detect microfilaments under native conditions. To visualise the spatial dynamics of actin we generated a parasite-specific actin antibody that shows preferential recognition of filamentous actin and applied this tool to different lifecycle stages (merozoites, sporozoites and ookinetes) of the human and mouse malaria parasite species Plasmodium falciparum and P. berghei along with tachyzoites from the related apicomplexan parasite Toxoplasma gondii. Actin filament distribution was found associated with three core compartments: the nuclear periphery, pellicular membranes of motile or invasive parasite forms and in a ring-like distribution at the tight junction during merozoite invasion of erythrocytes in both human and mouse malaria parasites. Localisation at the nuclear periphery is consistent with an emerging role of actin in facilitating parasite gene regulation. During invasion, we show that the actin ring at the parasite-host cell tight junction is dependent on dynamic filament turnover. Super-resolution imaging places this ring posterior to, and not concentric with, the junction marker rhoptry neck protein 4. This implies motor force relies on the engagement of dynamic microfilaments at zones of traction, though not necessarily directly through receptor-ligand interactions at sites of adhesion during invasion. Combined, these observations extend current understanding of the diverse roles actin plays in malaria parasite development and apicomplexan cell motility, in particular refining understanding on the linkage of the internal parasite gliding motor with the extra-cellular milieu. 相似文献
905.
906.
Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington's disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 and 2. A shared genetic basis, and overlapping clinical features for some of these diseases, indicate that common pathways may contribute to pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins and expanded repeat RNA, have been identified by the use of model systems, that may account for shared pathology. The use of such animal models enables identification of distinct pathways and their 'molecular hallmarks' that can be used to determine the contribution of each pathway in human pathology. Here we characterise a tergite disruption phenotype in adult flies, caused by ubiquitous expression of either untranslated CUG or CAG expanded repeat RNA. Using the tergite phenotype as a quantitative trait we define a new genetic system in which to examine 'hairpin' repeat RNA-mediated cellular perturbation. Further experiments use this system to examine whether pathways involving Muscleblind sequestration or Dicer processing, which have been shown to mediate repeat RNA-mediated pathology in other model systems, contribute to cellular perturbation in this model. 相似文献
907.
908.
DA Parry SJ Brookes CV Logan JA Poulter W El-Sayed S Al-Bahlani S Al Harasi J Sayed el M Raïf RC Shore M Dashash M Barron JE Morgan IM Carr GR Taylor CA Johnson MJ Aldred MJ Dixon JT Wright J Kirkham CF Inglehearn AJ Mighell 《American journal of human genetics》2012,91(3):565-571
Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis. 相似文献
909.
Infection of the bovine endometrium with Gram-negative bacteria commonly causes uterine disease. Toll-like receptor 4 (TLR4) on cells of the immune system bind Gram-negative bacterial lipopolysaccharide (LPS), stimulating the secretion of the proinflammatory cytokines interleukin 1B (IL1B) and IL6, and the chemokine IL8. Because the endometrium is the first barrier to infection of the uterus, the signaling cascade triggered by LPS and the subsequent expression of inflammatory mediators were investigated in endometrial epithelial and stromal cells, and the key pathways identified using short interfering RNA (siRNA) and biochemical inhibitors. Treatment of endometrial cells with ultrapure LPS stimulated an inflammatory response characterized by increased IL1B, IL6, and IL8 mRNA expression, and IL6 protein accumulation in epithelial cells, and by increased IL1B and IL8 mRNA expression, and IL6 and IL8 protein accumulation in stromal cells. Treatment of endometrial cells with LPS also induced the degradation of IKB and the nuclear translocation of NFKB, as well as rapid phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1) and MAPK14. Knockdown of TLR4 or its signaling adaptor molecule, myeloid differentiation factor 88 (MYD88), using siRNA reduced the inflammatory response to LPS in epithelial and stromal cells. Biochemical inhibition of MAPK3/1, but not JNK or MAPK14, reduced LPS-induced IL1B, IL6, and IL8 expression in endometrial cells. In conclusion, epithelial and stromal cells have an intrinsic role in innate immune surveillance in the endometrium, and in the case of LPS this recognition occurs via TLR4- and MYD88-dependent cell signaling pathways. 相似文献
910.
The chaperonin GroEL assists the folding of nascent or stress-denatured polypeptides by actions of binding and encapsulation. ATP binding initiates a series of conformational changes triggering the association of the cochaperonin GroES, followed by further large movements that eject the substrate polypeptide from hydrophobic binding sites into a GroES-capped, hydrophilic folding chamber. We used cryo-electron microscopy, statistical analysis, and flexible fitting to resolve a set of distinct GroEL-ATP conformations that can be ordered into a trajectory of domain rotation and elevation. The initial conformations are likely to be the ones that capture polypeptide substrate. Then the binding domains extend radially to separate from each other but maintain their binding surfaces facing the cavity, potentially exerting mechanical force upon kinetically trapped, misfolded substrates. The extended conformation also provides a potential docking site for GroES, to trigger the final, 100° domain rotation constituting the "power stroke" that ejects substrate into the folding chamber. 相似文献