全文获取类型
收费全文 | 208篇 |
免费 | 12篇 |
专业分类
220篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 11篇 |
2013年 | 18篇 |
2012年 | 7篇 |
2011年 | 16篇 |
2010年 | 14篇 |
2009年 | 12篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 20篇 |
2003年 | 12篇 |
2002年 | 8篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有220条查询结果,搜索用时 0 毫秒
101.
Vidya Latha Parsam Chitra Kannabiran Santosh Honavar Geeta K. Vemuganti Mohammad Javed Ali 《Journal of genetics》2009,88(4):517-527
Retinoblastoma (Rb) is the most common primary intraocular malignancy in children. It is brought about by the mutational inactivation
of both alleles of RB1 gene in the developing retina. To identify the RB1 mutations, we analysed 74 retinoblastoma patients by screening the exons and the promoter region of RB1. The strategy used was to detect large deletions/duplications by fluorescent quantitative multiplex PCR; small deletions/insertions
by fluorescent genotyping of RB1 alleles, and point mutations by PCR-RFLP and sequencing. Genomic DNA from the peripheral blood leucocytes of 74 Rb patients
(53 with bilateral Rb, 21 with unilateral Rb; 4 familial cases) was screened for mutations. Recurrent mutations were identified
in five patients with bilateral Rb, large deletions in 11 patients (nine with bilateral Rb and two with unilateral Rb), small
deletions/insertions were found in 12 patients all with bilateral Rb, and point mutations in 26 patients (14 nonsense, six
splice site, five substitution and one silent change). Three mutations were associated with variable expressivity of the disease
in different family members. Using this method, the detection rates achieved in patients with bilateral Rb were 44/53 (83%)
and with unilateral Rb, 5/21 (23.8%). This approach may be feasible for clinical genetic testing and counselling of patients. 相似文献
102.
Churamani D Geach TJ Ramakrishnan L Prideaux N Patel S Dale L 《The Journal of biological chemistry》2012,287(10):6974-6978
CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca(2+)-mobilizing second messengers. Although a variety of functions have been ascribed to CD38, such as immune responses, insulin secretion, and social behavior in adults, nothing is known of its role during embryonic development when Ca(2+) signals feature prominently. Here, we report the identification and functional expression of CD38 from Xenopus laevis, a key model organism for the study of vertebrate development. We show that CD38 expression and endogenous ADP-ribosyl cyclase activity are developmentally regulated during cellular differentiation. Chemical or molecular inhibition of CD38 abolished ADP-ribosyl cyclase activity and disrupted elongation of the anterior-posterior axis and differentiation of skeletal muscle, culminating in embryonic death. Our data uncover a previously unknown role for CD38 as an essential regulator of embryonic development. 相似文献
103.
Latha Rangan Halasya Meenakshisundaram Sankararamasubramanian Ragagopalan Radha Monkumbu Sambasivan Swaminathan 《Plant biosystems》2013,147(3):339-348
ABSTRACT Twenty-one species belonging to Oryza, including wild rices, were compared with a tetraploid (2n=48) halophytic wild rice relative, Porteresia coarctata Tateoka (=Oryza coarctata) for the genetic relatedness using AFLP and RAPD markers. Diploid and tetraploid groups were clearly separated except in the case of a few species where the clustering was unique and different. The molecular analysis has helped in positioning Porteresia in the vicinity of other wild rice species, and to better understand the pattern of species differentiation in Oryza. From our study, O. australiensis seems to be related to P. coarctata; thus, O. australiensis may be an effective “bridge” species in transferring genetic traits from P. coarctata to O. sativa. The usefulness of molecular marker systems for studying polymorphism and classification, and in clarifying genetic relationships between wild species has been confirmed. 相似文献
104.
Gupta Manish Kumar Chiranjivi Adarsh Kumar Dutta Tanmay Dubey Vikash Kumar Rangan Latha 《Biometals》2022,35(2):285-301
BioMetals - This study reports the synthesis and characterization of zinc derivatized 3,5-dihydroxy 4′, 7- dimethoxyflavone (DHDM-Zn) compound for the development of new antileishmanial... 相似文献
105.
Evgeniy N. Donev Marta Derba-Maceluch Zakiya Yassin Madhavi Latha Gandla Sivan Pramod Emilia Heinonen Vikash Kumar Gerhard Scheepers Francisco Vilaplana Ulf Johansson Magnus Hertzberg Björn Sundberg Sandra Winestrand Andreas Hörnberg Björn Alriksson Leif J. Jönsson Ewa J. Mellerowicz 《Plant biotechnology journal》2023,21(5):1005-1021
Trees constitute promising renewable feedstocks for biorefinery using biochemical conversion, but their recalcitrance restricts their attractiveness for the industry. To obtain trees with reduced recalcitrance, large-scale genetic engineering experiments were performed in hybrid aspen blindly targeting genes expressed during wood formation and 32 lines representing seven constructs were selected for characterization in the field. Here we report phenotypes of five-year old trees considering 49 traits related to growth and wood properties. The best performing construct considering growth and glucose yield in saccharification with acid pretreatment had suppressed expression of the gene encoding an uncharacterized 2-oxoglutarate-dependent dioxygenase (2OGD). It showed minor changes in wood chemistry but increased nanoporosity and glucose conversion. Suppressed levels of SUCROSE SYNTHASE, (SuSy), CINNAMATE 4-HYDROXYLASE (C4H) and increased levels of GTPase activating protein for ADP-ribosylation factor ZAC led to significant growth reductions and anatomical abnormalities. However, C4H and SuSy constructs greatly improved glucose yields in saccharification without and with pretreatment, respectively. Traits associated with high glucose yields were different for saccharification with and without pretreatment. While carbohydrates, phenolics and tension wood contents positively impacted the yields without pretreatment and growth, lignin content and S/G ratio were negative factors, the yields with pretreatment positively correlated with S lignin and negatively with carbohydrate contents. The genotypes with high glucose yields had increased nanoporosity and mGlcA/Xyl ratio, and some had shorter polymers extractable with subcritical water compared to wild-type. The pilot-scale industrial-like pretreatment of best-performing 2OGD construct confirmed its superior sugar yields, supporting our strategy. 相似文献
106.
Julia Pinkhasov M. Lucrecia Alvarez Latha B. Pathangey Teresa L. Tinder Hugh S. Mason Amanda M. Walmsley Sandra J. Gendler Pinku Mukherjee 《Cancer immunology, immunotherapy : CII》2010,59(12):1801-1811
Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the
efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated
whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant
mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB–MUC1 conjugate
along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen
tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance
in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB–MUC1 conjugate protein
and with the adjuvant CpG ODN co-delivered with CTB–MUC1. Importantly, mice immunized systemically with CpG ODN alone and
with CTB–MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1. 相似文献
107.
Katherine G. Hastings Powell O. Jose Kristopher I. Kapphahn Ariel T. H. Frank Benjamin A. Goldstein Caroline A. Thompson Karen Eggleston Mark R. Cullen Latha P. Palaniappan 《PloS one》2015,10(4)
Background
Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.Methods and Findings
We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer’s disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Conclusions
Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations. 相似文献108.
Scoparia dulcis (Sweet Broomweed) has been documented as a traditional treatment of diabetes. The administration of an aqueous extract of Scoparia dulcis at a dose of 200 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in streptozotocin diabetic rats at the end of 15 days treatment. The insulin secretagogue action of Scoparia dulcis plant extract (SPEt) was further investigated using isolated pancreatic islets from mice. SPEt at a dose of 10 microg/ml evoked 6.0 fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. In addition the effect of SPEt on streptozotocin induced cell death and nitric oxide (NO) in terms of nitrite production were also examined. SPEt protected against streptozotocin- mediated cytotoxicity (88%) and NO production in rat insulinoma cell line (RINm5F). Above results suggest the glucose lowering effect of SPEt to be associated with potentiation of insulin release from pancreatic islets. Our results revealed the possible therapeutic value of Scoparia dulcis for the better control, management and prevention of diabetes mellitus progression. 相似文献
109.
110.
Mucosal wound healing in adults has been reported to feature diminished scar formation compared to healing skin wounds. We
sought to determine if the expression pattern of chaperonin containing T-complex polypeptide (CCT) subunits in mucosal wounds
and fibroblasts is different from that observed in skin wounds and fibroblasts. We found that CCT-beta is the only subunit
message to be reduced in wounded mucosa versus unwounded control, and this reduction was confirmed at the protein level. In
contrast, mRNA levels of CCT-zeta, -delta, -eta, and -epsilon were significantly increased in mucosal wounds. The increase
in CCT-eta was also confirmed at the protein level. Expression levels of CCT-alpha, -beta, -delta; -epsilon, and -theta mRNAs
were significantly increased in adult mucosal fibroblasts in culture compared to skin-derived fibroblasts. Western blot analyses
confirmed a modest increase in CCT-beta in adult mucosal fibroblasts relative to skin fibroblasts, but CCT-eta protein was
unaffected. These differences may contribute to the reported difference in healing outcomes between these two tissue types. 相似文献