全文获取类型
收费全文 | 1424篇 |
免费 | 106篇 |
专业分类
1530篇 |
出版年
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 19篇 |
2020年 | 14篇 |
2019年 | 24篇 |
2018年 | 38篇 |
2017年 | 29篇 |
2016年 | 57篇 |
2015年 | 54篇 |
2014年 | 77篇 |
2013年 | 105篇 |
2012年 | 98篇 |
2011年 | 94篇 |
2010年 | 74篇 |
2009年 | 66篇 |
2008年 | 93篇 |
2007年 | 58篇 |
2006年 | 69篇 |
2005年 | 92篇 |
2004年 | 73篇 |
2003年 | 59篇 |
2002年 | 60篇 |
2001年 | 27篇 |
2000年 | 8篇 |
1999年 | 18篇 |
1998年 | 13篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 9篇 |
1991年 | 11篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1971年 | 2篇 |
1957年 | 2篇 |
排序方式: 共有1530条查询结果,搜索用时 15 毫秒
31.
Maria Rosaria Faraone-Mennella Anna Petrella Francesco Manguso Rosario Peluso Benedetta Farina 《Biomarkers》2013,18(6):381-387
The clinical usefulness of an immunotest was evaluated by using purified poly(adenosine diphosphate (ADP)-ribose) polymerase from Sulfolobus solfataricus (PARPSso) as an antigen to detect the presence of abnormal anti-PARP antibodies in the sera of patients with systemic lupus erythematosus (SLE) at different clinical stages. Sera from 44 patients with SLE, subgrouped on the basis of disease activity (16 with inactive disease, 28 with active disease) were analysed with a new immunotest to detect anti-PARP antibodies, and with an immunofluorescent (IIF) assay for antinuclear antibodies (ANA) detection. ANA detection by IIF revealed that sera of healthy subjects were negative, whereas sera from patients with SLE were positive in all cases (13 positive at 1:80, 15 at 1:160, 15 at 1:320, 1 at 1:640, v/v). Anti-PARP activity was higher in ANA-positive patients than in controls (p?=?0.005). Within the group of SLE sera, disease and anti-PARP activity was increased more significantly in patients with active than in those with inactive disease (p?0.001 and p?=?0.001, respectively). Correlation between anti-PARP and disease activity in SLE patients was statistically significant (p?0.001). PARPSso seems to be suitable for detecting anti-PARP antibodies and could play a role as a serological marker of disease activity in patients with SLE. 相似文献
32.
Rosario Vecchio Salvatore Marchese Francesco Ferla Linda Spataro Eva Intagliata 《Parasitology international》2013,62(6):487-493
BackgroundSolitary subcutaneous hydatid cyst is not frequent and the only symptom is generally a silent growing mass. Total excision remains the mainstay of treatment. Aim of the study was to present a case surgically treated and perform a statistical analysis reviewing previous published works in order to define a correct approach to diagnosis and treatment.Methods264 documents from Medline database were considered for primary subcutaneous hydatid cyst cases. Data concerning geographic region, gender, age, job, location, evolving time, history and physical, mobility, diameter, laboratory, imaging, locularity (uni- or multilocular cyst), fine-needle aspiration, preoperative diagnosis, neoadjuvant chemotherapy, treatment, spillage, adjuvant therapy, follow-up and recurrences were ordered in a database and analysed performing t-test, Fisher's test and Pearson's test.Results23 cases, included ours, resulted suitable for our study. Lower extremities were involved in most cases (60.9%) and the thigh represented the most common site (34.8%), whereas upper extremities were the rarest location (8.7%). Patients with head and neck located cysts were younger than those with upper extremities cysts (P = 0.037). Patients who underwent multiple imaging approach received a significantly correct first diagnosis (P = 0.001) and ultrasonography, unlike other techniques, appeared to be essential (P = 0.013).Case reportA 68-year-old man who lived and worked in his farm in Sicily (Italy) presented with a 30-year-growing mass in the deltoid region measuring 10 cm. Ultrasonography and magnetic resonance imaging strongly suggested hydatid cyst. Therefore the cyst was excised and pathology confirmed the diagnosis.ConclusionSolitary subcutaneous hydatid cyst must always be considered in the differential diagnosis of silent growing mass in soft tissues. History and physical associated with ultrasound and magnetic resonance imaging are sufficient to achieve a correct preoperative diagnosis. 相似文献
33.
34.
Ruth Muchekehu Dingguo Liu Mark Horn Lioudmila Campbell Joselyn Del Rosario Michael Bacica Haim Moskowitz Trina Osothprarop Anouk Dirksen Venkata Doppalapudi Allan Kaspar Steven R. Pirie-Shepherd Julia Coronella 《Translational oncology》2013,6(5):562-IN6
Poor drug delivery and penetration of antibody-mediated therapies pose significant obstacles to effective treatment of solid tumors. This study explored the role of pharmacokinetics, valency, and molecular weight in maximizing drug delivery. Biodistribution of a fibroblast growth factor receptor 4 (FGFR4) targeting CovX-body (an FGFR4-binding peptide covalently linked to a nontargeting IgG scaffold; 150 kDa) and enzymatically generated FGFR4 targeting F(ab)2 (100 kDa) and Fab (50 kDa) fragments was measured. Peak tumor levels were achieved in 1 to 2 hours for Fab and F(ab)2versus 8 hours for IgG, and the percentage injected dose in tumors was 0.45%, 0.5%, and 2.5%, respectively, compared to 0.3%, 2%, and 6% of their nontargeting controls. To explore the contribution of multivalent binding, homodimeric peptides were conjugated to the different sized scaffolds, creating FGFR4 targeting IgG and F(ab)2 with four peptides and Fab with two peptides. Increased valency resulted in an increase in cell surface binding of the bivalent constructs. There was an inverse relationship between valency and intratumoral drug concentration, consistent with targeted consumption. Immunohistochemical analysis demonstrated increased size and increased cell binding decreased tumor penetration. The binding site barrier hypothesis suggests that limited tumor penetration, as a result of high-affinity binding, could result in decreased efficacy. In our studies, increased target binding translated into superior efficacy of the IgG instead, because of superior inhibition of FGFR4 proliferation pathways and dosing through the binding site barrier. Increasing valency is therefore an effective way to increase the efficacy of antibody-based drugs. 相似文献
35.
Julio Plaza-Diaz Carolina Gomez-Llorente Laura Campa?a-Martin Esther Matencio Inmaculada Ortu?o Rosario Martínez-Silla Carlos Gomez-Gallego Maria Jesús Periago Gaspar Ros Empar Chenoll Salvador Genovés Beatriz Casinos ángela Silva Dolores Corella Olga Portolés Fernando Romero Daniel Ramón Antonio Perez de la Cruz Angel Gil Luis Fontana 《PloS one》2013,8(10)
We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.
Trial Registration
ClinicalTrials.gov NCT01479543 相似文献36.
37.
M. Rosario Darquier Cecilia F. Bessega Mariano Cony Juan C. Vilardi Beatriz O. Saidman 《Tree Genetics & Genomes》2013,9(1):307-320
Prosopis flexuosa is an arboreal Leguminosae that grows in arid and semiarid temperate zones of Argentina, in the Monte eco-region. It is a promising native forest species for recovering arid and semiarid regions because it plays an important role in erosion control as well as in soil fertility. Furthermore, it provides diverse economical resources. The main challenge to the forestry sector is finding a balance between production and forest protection. For this purpose, it is necessary to gather information about genetic parameters. In this study, we measured the distribution of the variation of 14 quantitative traits in an experimental half-sib stand, where families are representative of hierarchically structured populations. We applied a multivariate extension of the classical Q ST –F ST neutrality test to determine the relative importance of drift versus selection in the distribution of genetic variability. We found strong evidence that different selective regimes act on different traits and that selection favors different optima in each sampling site. The selection to different optima is much stronger among than within provenances. This result helps explain the possible causes for the regional variation observed in P. flexuosa and to define the management units and the evolutionarily significant units for this species. 相似文献
38.
39.
40.
Sebastián Hernán Sarnacki María del Rosario Aya Casta?eda Mariángeles Noto Llana Mónica Nancy Giacomodonato Miguel ángel Valvano María Cristina Cerquetti 《PloS one》2013,8(2)
The absence of Dam in Salmonella enterica serovar Enteritidis causes a defect in lipopolysaccharide (LPS) pattern associated to a reduced expression of wzz gene. Wzz is the chain length regulator of the LPS O-antigen. Here we investigated whether Dam regulates wzz gene expression through its two known regulators, PmrA and RcsB. Thus, the expression of rcsB and pmrA was monitored by quantitative real-time RT-PCR and Western blotting using fusions with 3×FLAG tag in wild type (wt) and dam strains of S. Enteritidis. Dam regulated the expression of both rcsB and pmrA genes; nevertheless, the defect in LPS pattern was only related to a diminished expression of RcsB. Interestingly, regulation of wzz in serovar Enteritidis differed from that reported earlier for serovar Typhimurium; RcsB induces wzz expression in both serovars, whereas PmrA induces wzz in S. Typhimurium but represses it in serovar Enteritidis. Moreover, we found that in S. Enteritidis there is an interaction between both wzz regulators: RcsB stimulates the expression of pmrA and PmrA represses the expression of rcsB. Our results would be an example of differential regulation of orthologous genes expression, providing differences in phenotypic traits between closely related bacterial serovars. 相似文献