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41.
José R. Santos José A. Mu?oz-Moreno José Moltó Anna Prats Adrià Curran Pere Domingo Josep M. Llibre Daniel R. McClernon Isabel Bravo Jaume Canet Victoria Watson David Back Bonaventura Clotet 《PloS one》2013,8(7)
Background
Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited.Methods
Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons.Results
Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012).Conclusions
Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning. 相似文献42.
Barbara G Schneider M Blanca Piazuelo Liviu A Sicinschi Robertino Mera Dun-Fa Peng Juan Carlos Roa Judith Romero-Gallo Alberto G Delgado Thibaut de Sablet Luis E Bravo Keith T Wilson Wael El-Rifai Richard M Peek Jr Pelayo Correa 《Epigenetics》2013,8(11):1153-1161
DNA methylation changes are known to occur in gastric cancers and in premalignant lesions of the gastric mucosae. In order to examine variables associated with methylation levels, we quantitatively evaluated DNA methylation in tumors, non-tumor gastric mucosae, and in gastric biopsies at promoters of 5 genes with methylation alterations that discriminate gastric cancers from non-tumor epithelia (EN1, PCDH10, RSPO2, ZIC1, and ZNF610). Among Colombian subjects at high and low risk for gastric cancer, biopsies from subjects from the high-risk region had significantly higher levels of methylation at these 5 genes than samples from subjects in the low risk region (p ≤ 0.003). When results were stratified by Helicobacter pylori infection status, infection with a cagA positive, vacA s1m1 strain was significantly associated with highest methylation levels, compared with other strains (p = 0.024 to 0.001). More severe gastric inflammation and more advanced precancerous lesions were also associated with higher levels of DNA methylation (p ≤ 0.001). In a multivariate model, location of residence of the subject and the presence of cagA and vacA s1m1 in the H. pylori strain were independent variables associated with higher methylation in all 5 genes. High levels of mononuclear cell infiltration were significantly related to methylation in PCDH10, RSPO2, and ZIC1 genes. These results indicate that for these genes, levels of methylation in precancerous lesions are related to H. pylori virulence, geographic region and measures of chronic inflammation. These genes seem predisposed to sustain significant quantitative changes in DNA methylation at early stages of the gastric precancerous process. 相似文献
43.
LEA Gene Introns: is the Intron of Dehydrin Genes a Characteristic of the Serine-Segment? 总被引:1,自引:0,他引:1
Juan Francisco Jiménez-Bremont Israel Maruri-López Ana Erika Ochoa-Alfaro Pablo Delgado-Sánchez Jaime Bravo Margarita Rodríguez-Kessler 《Plant Molecular Biology Reporter》2013,31(1):128-140
Dehydrins, which belong to group 2 LEA proteins, are a family of intrinsically unstructured plant proteins that accumulate during the late stages of embryogenesis and in response to abiotic stresses. We have previously reported that the OpsDHN1 gene, encoding an SK3-type acidic dehydrin protein from Opuntia streptacantha, contains an intron inserted within the sequence encoding the S-motif. Herein, we present an in silico analysis of intron sequences in dehydrin genes from mono- and dicotyledonous plants that reveals a preference for insertion within the nucleotide sequence encoding the S-motif. Sequence comparison of ten Dhn genes from Arabidopsis thaliana and the orthologous genes in Arabidopsis lyrata revealed that introns maintain considerable sequence identity and conserve the insertion pattern. Furthermore, syntenic regions were identified among eight orthologous genes of A. thaliana and A. lyrata, showing that correlated gene arrangements are conserved between these Arabidopsis species. Our study shows that most SKn-type dehydrins contain one intron that is conserved in phase and location; this intron is linked to the nucleotide sequence that encodes the S-motif. 相似文献
44.
45.
Andrea Gómez Bravo María Gabriela Quintana Marcelo Abril Oscar Daniel Salomón 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1071-1073
In 2004, the urban presence of Lutzomyia longipalpis was recorded
for the first time in Formosa province. In 2006, the first autochthonous case of
human urban visceral leishmaniasis (VL) was recorded in Misiones in the presence of
the vector, along with some canine VL cases. After this first case, the vector began
to spread primarily in northeast Argentina. Between 2008-2011, three human VL cases
were reported in Salta province, but the presence of Lu. longipalpis
was not recorded. Captures of Phlebotominae were made in Tartagal, Salta, in 2013,
and the presence of Lu. longipalpis was first recorded in northwest
Argentina at that time. Systematic sampling is recommended to observe the
distribution and dispersion patterns of Lu. longipalpis and consider
the risk of VL transmission in the region. 相似文献
46.
47.
Miriam Andrés Mónica Bravo Maria Antonia Buil Marta Calbet Jordi Castro Teresa Domènech Peter Eichhorn Manel Ferrer Elena Gómez Martin D. Lehner Imma Moreno Richard S. Roberts Sara Sevilla 《Bioorganic & medicinal chemistry letters》2013,23(11):3349-3353
High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors. 相似文献
48.
Issam Arrouss Fariba Nemati Fernando Roncal Marie Wislez Karim Dorgham David Vallerand Nathalie Rabbe Narjesse Karboul Fran?oise Carlotti Jeronimo Bravo Dominique Mazier Didier Decaudin Angelita Rebollo 《PloS one》2013,8(4)
Purpose
PP2A is a serine/threonine phosphatase critical to physiological processes, including apoptosis. Cell penetrating peptides are molecules that can translocate into cells without causing membrane damage. Our goal was to develop cell-penetrating fusion peptides specifically designed to disrupt the caspase-9/PP2A interaction and evaluate their therapeutic potential in vitro and in vivo.Experimental Design
We generated a peptide containing a penetrating sequence associated to the interaction motif between human caspase-9 and PP2A (DPT-C9h), in order to target their association. Using tumour cell lines, primary human cells and primary human breast cancer (BC) xenografts, we investigated the capacity of DPT-C9h to provoke apoptosis in vitro and inhibition of tumour growth (TGI) in vivo. DPT-C9h was intraperitonealy administered at doses from 1 to 25 mg/kg/day for 5 weeks. Relative Tumour Volume (RTV) was calculated.Results
We demonstrated that DPT-C9h specifically target caspase-9/PP2A interaction in vitro and in vivo and induced caspase-9-dependent apoptosis in cancer cell lines. DPT-C9h also induced significant TGI in BC xenografts models. The mouse-specific peptide DPT-C9 also induced TGI in lung (K-Ras model) and breast cancer (PyMT) models. DPT-C9h has a specific effect on transformed B cells isolated from chronic lymphocytic leukemia patients without any effect on primary healthy cells. Finally, neither toxicity nor immunogenic responses were observed.Conclusion
Using the cell-penetrating peptides blocking caspase-9/PP2A interactions, we have demonstrated that DPT-C9h had a strong therapeutic effect in vitro and in vivo in mouse models of tumour progression. 相似文献49.
50.
Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer
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Maria Jesús Fernández‐Aceñero Aurea Borrero‐Palacios Laura del Puerto‐Nevado Javier Martínez‐Useros Juan Pablo Marín‐Arango Cristina Caramés Ricardo Vega‐Bravo María Rodríguez‐Remírez Marlid Cruz‐Ramos Félix Manzarbeitia Jesús García‐Foncillas 《Journal of cellular and molecular medicine》2016,20(9):1729-1736
Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio‐ and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre‐treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease‐free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. 相似文献