全文获取类型
收费全文 | 210篇 |
免费 | 6篇 |
专业分类
216篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 7篇 |
2013年 | 21篇 |
2012年 | 5篇 |
2011年 | 15篇 |
2010年 | 10篇 |
2009年 | 10篇 |
2008年 | 9篇 |
2007年 | 14篇 |
2006年 | 11篇 |
2005年 | 11篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1968年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有216条查询结果,搜索用时 15 毫秒
131.
132.
F. Daprà † F. Gai M. T. Costanzo ‡ G. Maricchiolo ‡ V. Micale ‡ B. Sicuro § G. Caruso ‡ L. Genovese ‡ G. B. Palmegiano 《Journal of fish biology》2009,74(4):773-789
Field and laboratory studies were conducted to evaluate the intestinal responses to partial replacement of fish meal with rice protein concentrate (RPC) in practical diets for blackspot seabream Pagellus bogaraveo . Two experimental diets were formulated to be isoproteic and isoenergetic with an increasing level of RPC (20 and 35%, respectively) and were tested against a fish meal-based control diet (RPC0). The diets showed similar features for growth performances and both intestinal histology and digestive enzymes. This study confirmed that RPC does not induce intestinal mucosa alterations in this fish. The dietary RPC supplement caused a significant increase in trypsin activity, whereas lipase activity was reduced. 相似文献
133.
Bhatia G Patterson N Pasaniuc B Zaitlen N Genovese G Pollack S Mallick S Myers S Tandon A Spencer C Palmer CD Adeyemo AA Akylbekova EL Cupples LA Divers J Fornage M Kao WH Lange L Li M Musani S Mychaleckyj JC Ogunniyi A Papanicolaou G Rotimi CN Rotter JI Ruczinski I Salako B Siscovick DS Tayo BO Yang Q McCarroll S Sabeti P Lettre G De Jager P Hirschhorn J Zhu X Cooper R Reich D Wilson JG Price AL 《American journal of human genetics》2011,89(3):368-381
The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (FST < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10−11) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers. 相似文献
134.
Scanning and transmission electron microscopy were used to investigate the fine structure of the sperm of the sparid fish Pagellus bogaraveo.The spermatozoon of P. bogaraveo belongs, like that of the other sparid fish, to the teleostean “type I” spermatozoon with the flagellar axis insert perpendicular to the nuclear fossa. It has an ovoidal head, a short, cylindrically shaped midpiece and a long tail region. The nucleus reveals a deep invagination (nuclear fossa), in which the centriolar complex is located, and a satellite nuclear notch shaped like a golf club. The two centrioles are perpendicular to each other and show a conventional “9+0” pattern. The distal centriole is attached to the nuclear envelope by means of basal feet and radial fibers made of electron-dense material. Below the basal plate, plasma membrane pinches in, and the necklace, a specialized connection joining axonemal doublets to the plasma membrane, is visible. The short midpiece houses one mitochondrion. The flagellum is perpendicularly and eccentrically with respect to the nucleus and contains the conventional “9+2” axoneme. 相似文献
135.
Fiorito Serena Preziuso Francesca Sharifi-Rad Majid Marchetti Lorenzo Epifano Francesco Genovese Salvatore 《Phytochemistry Reviews》2022,21(2):317-326
Phytochemistry Reviews - Auraptene and umbelliprenin are among the most abundant naturally occurring prenyloxy umbelliferone derivatives. Both have been mainly isolated from plants belonging to... 相似文献
136.
Denaro R D'Auria G Di Marco G Genovese M Troussellier M Yakimov MM Giuliano L 《Environmental microbiology》2005,7(1):78-87
The distribution of bacterial communities terminal restriction fragment length polymorphism (T-RFLP) fingerprint patterns was evaluated at three proximal hydrocarbon-contaminated sites located within the harbour of Messina. In order to analyse the short-term variability of the individual terminal restriction fragment (T-RF) patterns, water samples were collected at the three sites on three occasions within 3 months (T(0), T(90) and T(91)). Four sample sizes, from 50 to 1000 ml for each collected sample, were analysed separately (36 total analysed samples) to evaluate the relationship between the sample size and the bacterial diversity estimates. The dominant T-RF groups mostly belonged to signatures of putative hydrocarbon-degrading bacteria, as revealed by the virtual analysis of the obtained bands. In order to test whether significant differences were occurring between the analysed samples, the Kruskal-Wallis non-parametric test was applied to the T-RF data set. Neither significant influence of the sample size nor short spatial variability within the three sampled sites was detected for each sampling time. On the contrary, significant temporal changes in the diversity of the bacterial communities were observed. These results were confirmed by the non-metric multidimensional scales (nMDS) analysis of the whole set of samples, which indicated three main groups corresponding to the three different sampling times. In summary, the T-RFLP technique, although a polymerase chain reaction-based method, proved to be a suitable technique for monitoring polluted marine environments, typically characterized by low diversity and high relative abundances of a few dominant groups. 相似文献
137.
The present study is focused on the characterization of the interaction between trimethoprim, a dihydropteroate synthesase inhibitor, and hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solution and solid state. The freeze-drying method was used to prepare solid complexes, while simple blending was employed to obtain physical mixtures. The phase solubility was AN type, and demonstrated that trimethoprim solubility was significantly increased upon complexation with HP-β-CD. Conductivity experiments showed the presence of aggregates that explains the type profile for the solubility isotherm. The critical concentration for the aggregate formation was determined to be 69.3 mg/ml for pure HP-β-CD and 117.7 mg/ml in the presence of trimethoprim. Nuclear magnetic resonance spectroscopy provided evidence of trimethoprim:HP-β-CD molecular interaction in solution. Moreover, the complex was characterized in solid stated using Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The use of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the thermal stability of the drug is enhanced in the presence of HP-β-CD. 相似文献
138.
Palmieri G Acone F Desantis S Corriero A Ventriglia G Addis P Genovese S Aprea A Spedicato D Losurdo M Deflorio M Di Summa A De Metrio G 《European journal of histochemistry : EJH》2008,52(1):19-28
The present study was focused on the morphology of the diencephalic nuclei (likely involved in reproductive functions) as well as on the distribution of GnRH (gonadotropin-releasing hormone) in the rhinencephalon, telencephalon and the diencephalon of the brain of bluefin tuna (Thunnus thynnus) by means of immunohistochemistry. Bluefin tuna has an encephalization quotient (QE) similar to that of other large pelagic fish. Its brain exhibits well-developed optic tecta and corpus cerebelli. The diencephalic neuron cell bodies involved in reproductive functions are grouped in two main nuclei: the nucleus preopticus-periventricularis and the nucleus lateralis tuberis. The nucleus preopticus-periventricularis consists of the nucleus periventricularis and the nucleus preopticus consisting of a few sparse multipolar neurons in the rostral part and numerous cells closely packed and arranged in several layers in its aboral part. The nucleus lateralis tuberis is located in the ventral-lateral area of the diencephalon and is made up of a number of large multipolar neurones. Four different polyclonal primary antibodies against salmon (s)GnRH, chicken (c)GnRH-II (cGnRH-II 675, cGnRH-II 6) and sea bream (sb)GnRH were employed in the immunohistochemical experiments. No immunoreactive structures were found with anti sbGnRH serum. sGnRH and cGnRH-II antisera revealed immunoreactivity in the perikarya of the olfactory bulbs, preopticus-periventricular nucleus, oculomotor nucleus and midbrain tegmentum. The nucleus lateralis tuberis showed immunostaining only with anti-sGnRH serum. Nerve fibres immunoreactive to cGnRH and sGnRH sera were found in the olfactory bulbs, olfactory nerve and neurohypophysis. The significance of the distribution of the GnRH-immunoreactive neuronal structures is discussed. 相似文献
139.
Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery 总被引:9,自引:0,他引:9
Lombardo A Genovese P Beausejour CM Colleoni S Lee YL Kim KA Ando D Urnov FD Galli C Gregory PD Holmes MC Naldini L 《Nature biotechnology》2007,25(11):1298-1306
Achieving the full potential of zinc-finger nucleases (ZFNs) for genome engineering in human cells requires their efficient delivery to the relevant cell types. Here we exploited the infectivity of integrase-defective lentiviral vectors (IDLV) to express ZFNs and provide the template DNA for gene correction in different cell types. IDLV-mediated delivery supported high rates (13-39%) of editing at the IL-2 receptor common gamma-chain gene (IL2RG) across different cell types. IDLVs also mediated site-specific gene addition by a process that required ZFN cleavage and homologous template DNA, thus establishing a platform that can target the insertion of transgenes into a predetermined genomic site. Using IDLV delivery and ZFNs targeting distinct loci, we observed high levels of gene addition (up to 50%) in a panel of human cell lines, as well as human embryonic stem cells (5%), allowing rapid, selection-free isolation of clonogenic cells with the desired genetic modification. 相似文献
140.
Vibeke Strand Mark Kosinski Chieh-I Chen George Joseph Regina Rendas-Baum Neil M. H. Graham Hubert van Hoogstraten Martha Bayliss Chunpeng Fan Tom Huizinga Mark C. Genovese 《Arthritis research & therapy》2016,18(1)
BackgroundSarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT.MethodsPatients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24.ResultsBoth doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores.ConclusionsIn this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab.