全文获取类型
收费全文 | 653篇 |
免费 | 37篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 11篇 |
2019年 | 13篇 |
2018年 | 14篇 |
2017年 | 13篇 |
2016年 | 17篇 |
2015年 | 52篇 |
2014年 | 40篇 |
2013年 | 45篇 |
2012年 | 63篇 |
2011年 | 61篇 |
2010年 | 32篇 |
2009年 | 35篇 |
2008年 | 34篇 |
2007年 | 35篇 |
2006年 | 35篇 |
2005年 | 30篇 |
2004年 | 24篇 |
2003年 | 30篇 |
2002年 | 18篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有690条查询结果,搜索用时 31 毫秒
131.
Larry M. Palato Shannon Pilcher Alissa Oakes Arleen Lamba Jaris Torres Litza I. Ledesma Monjaraz Crystabel Munoz Edward Njoo Dillon J. Rinauro Kate Alexandra Menefee Angela Tun Betssy L. Jauregui Sarah Shapiro Olivia H. Nossiff Eileen Olivares Kevin Chang Viviane Nguyen Luiza A. Nogaj David A. Moffet 《Journal of peptide science》2019,25(8)
The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP. 相似文献
132.
Colussi F Serpa V Delabona Pda S Manzine LR Voltatodio ML Alves R Mello BL Pereira N Farinas CS Golubev AM Santos MA Polikarpov I 《Journal of microbiology and biotechnology》2011,21(8):808-817
Because of its elevated cellulolytic activity, the filamentous fungus Trichoderma harzianum has a considerable potential in biomass hydrolysis applications. Trichoderma harzianum cellobiohydrolase I (ThCBHI), an exoglucanase, is an important enzyme in the process of cellulose degradation. Here, we report an easy single-step ion-exchange chromatographic method for purification of ThCBHI and its initial biophysical and biochemical characterization. The ThCBHI produced by induction with microcrystalline cellulose under submerged fermentation was purified on DEAE-Sephadex A-50 media and its identity was confirmed by mass spectrometry. The ThCBHI biochemical characterization showed that the protein has a molecular mass of 66 kDa and pI of 5.23. As confirmed by smallangle X-ray scattering (SAXS), both full-length ThCBHI and its catalytic core domain (CCD) obtained by digestion with papain are monomeric in solution. Secondary structure analysis of ThCBHI by circular dichroism revealed alpha- helices and beta-strands contents in the 28% and 38% range, respectively. The intrinsic fluorescence emission maximum of 337 nm was accounted for as different degrees of exposure of ThCBHI tryptophan residues to water. Moreover, ThCBHI displayed maximum activity at pH 5.0 and temperature of 50 degrees C with specific activities against Avicel and p-nitrophenyl-β-D-cellobioside of 1.25 U/mg and 1.53 U/mg, respectively. 相似文献
133.
Lu Barbalho de Macêdo Marcela dos Santos Magalhes Lucas Castanhola Dias Khelven Klay de Azevedo Lemos Ryshely Sonaly de Moura Borges Mrcia Viviane Alves Saraiva Moacir Franco de Oliveira Antnio Chaves de Assis Neto Carlos Eduardo Bezerra de Moura 《Animal Reproduction》2022,19(3)
Sex steroid hormones are critical in gonadal differentiation in turtles. The gonads are not the only organs responsible for producing these hormones during this phase. Mesonephros play an important role in steroidogenesis. The present study aimed to investigate the presence of steroidogenic cells in mesonephros of Podocnemis expansa during gonadal differentiation and to evaluate their morphology and ultrastructure. Ten embryos of P. expansa were collected from 5 nests on day 36 of incubation, during spawning period on an artificial beach. Embryos were extracted from eggs by slicing the shell and euthanized. They were dissected under a stereoscopic microscope to collect the gonad-mesonephro complex, in which were fixed and subsequently processed for light microscopy, immunohistochemistry and transmission electron microscopy analysis. During histological analysis was observed mesonephros has typical morphological structure. Immunohistochemistry showed immunoreaction to aromatase in cells of intertubular space. Confirming these findings, it was possible to observe a type of intertubular cell in several regions of mesonephro, being more predominant in region close to blood vessels, distal and proximal tubules. In ultrastructural analysis these cells were characterized by having a clear, large, and rounded nucleus with evident nucleolus and cytoplasm rich in electron-dense droplets. This study demonstrated for the first time the presence of cells with morphological, immunohistochemical and ultrastructural characteristics similar to steroid-producing cells in P. expansa mesonephrons, suggesting that this organ may contribute to gonadal differentiation in this species. 相似文献
134.
Rachel Sarig Viviane Slon Janan Abbas Hila May Nir Shpack Alexander Dan Vardimon Israel Hershkovitz 《PloS one》2013,8(11)
Malocclusions are common in modern populations. Yet, as the study of occlusion requires an almost intact dentition in both the maxilla and mandible, searching for the ultimate cause of malocclusion is a challenge: relatively little ancient material is available for research on occlusal states. The Qafzeh 9 skull is unique, as its preserved dentition allowed us to investigate the presence and manifestations of malocclusion. The aim of this study was thus to examine the occlusal condition in the Qafzeh 9 specimen in light of modern knowledge regarding the etiology of malocclusion. We revealed a pathologic occlusion in the Qafzeh 9 skull that probably originated in the early developmental stage of the dentition, and was aggravated by forces applied by mastication. When arch continuity is interrupted due to misalignment of teeth as in this case, force transmission is not equal on both sides, causing intra-arch outcomes such as mesialization of the teeth, midline deviation, rotations and the aggravation of crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the left; the incisors rotate mesio-buccally; the left segment is constricted; the left first molar is buccally positioned and the left premolars palatally tilted. The inter-arch evaluation revealed anterior cross bite with functional shift that might affect force transmission and bite force. In conclusion, the findings of the current study suggest that malocclusion of developmental origin was already present in early anatomically modern humans (AMH) (the present case being the oldest known case, dated to ca. 100,000 years); that there is no basis to the notion that early AMH had a better adjustment between teeth and jaw size; and that jaw-teeth size discrepancy could be found in prehistoric populations and is not a recent phenomenon. 相似文献
135.
Carolina Costola-de-Souza Alison Ribeiro Viviane Ferraz-de-Paula Atilio Sersun Calefi Thiago Pinheiro Arrais Aloia Jo?o Antonio Gimenes-Júnior Vinicius Izidio de Almeida Milena Lob?o Pinheiro Jo?o Palermo-Neto 《PloS one》2013,8(10)
Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG), is mediated by monoacylglycerol lipase (MAGL). The piperidine carbamate, 4-nitrophenyl- 4-(dibenzo[d] [1,3]dioxol-5-yl (hydroxy) methyl) piperidine- 1-carboxylate (JZL184), is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p.)) of JZL184, in a murine model of lipopolysaccharide (LPS) -induced acute lung injury (ALI) 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL) and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) and the AM630 selective CB2 receptor antagonist ([6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)-methanone) blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors. 相似文献
136.
Gerardo H. Vzquez Nin Sousan Abolhassani-Dadras Olga M Echeverría Viviane Boutinard Rouelle-Rossier Stanislav Fakan 《Biology of the cell / under the auspices of the European Cell Biology Organization》1996,87(3):171-177
Summary— The in situ distribution of phosphorus in perichromatin granules (PCGs), and in the surrounding nucleoplasm was investigated in rat liver cells by means of electron spectroscopic imaging of unstained preparations. A 2–3 nm fibril containing high concentration of phosphorus was found to be the main substructural feature of the PCGs revealed in the maps of phosphorus. This fibril is folded within the PCG with no apparent order. Fibrils of similar diameter and phosphorus content were also found in both the halo surrounding the PCG and dispersed in the nucleoplasm. Some of such fibrils are in continuity with those occurring within PCGs. Sometimes these fibrils are grouped forming a stalk connecting the PCG to chromatin. Some stalked PCGs are U-shaped or kidneyshaped, resembling Balbiani ring granules in the process of formation as observed in Chironomus salivary gland cell nuclei. The external fibrils are interpreted as perichromatin fibrils considered to be precursors of PCGs. 相似文献
137.
Development of two PCR assays for the identification of mycoplasmas causing contagious agalactia 总被引:1,自引:0,他引:1
Laurence Dedieu Viviane Mady Pierre-Charles Lefevre 《FEMS microbiology letters》1995,129(2-3):243-249
Abstract A new detection test for the mycoplasmas causing contagious agalactia, Mycoplasma agalactiae , M. capricolum subsp. capricolum and M. mycoides subsp. mycoldes L.C., was developed. It was based on two polymerase chain reaction assays: the Ma-PCR for the detection of M. agalactiae and the MYC-PCR for the 'mycoides cluster' thus including M. capricolum subsp. capricolum and M. mycoides subsp. mycoides L.C. An M. agalactiae strain was identified by a 933-bp Ma-PCR product and no amplification with the MYC-PCR. In contrast, a 460-bp MYC-PCR product and a negative or a 350-bp Ma-PCR product characterized a 'mycoides cluster' strain. M. capricolum subsp. capricolum and M. mycoides subsp. mycoides L.C. were identified by their species-specific Asel pattern of the 460-bp MYC-PCR product. 相似文献
138.
Staphylococcus pasteuri-specific oligonucleotide probes derived from a random amplified DNA fragment 总被引:4,自引:0,他引:4
François Vandenesch Jean-David Perrier-Gros-Claude Michèle Bes Christine Fuhrmann Viviane Delorme Christiane Mouren Jerome Etienne 《FEMS microbiology letters》1995,132(1-2):147-152
Abstract A rapid polymerase chain reaction method was developed to differentiate Staphylococcus pasteuri from other staphylococcal species, especially the phenotypically similar S. warneri . The oligonucleotide probes used as primers were designed from the sequence of a S. pasteuri random amplified polymorphic DNA fragment. 相似文献
139.
140.
Viviane Dumur Elisabeth Trivier Bernard Puech Frédéric Peugnet Xavier Zanlonghi Jean Claude Hache André Hanauer 《Human genetics》1995,96(1):79-82
The gene involved in juvenile retinoschisis (RS) has previously been localized, by genetic linkage analyses, to Xp22.1-p22.2, between DXS274 and DXS43/ DXS207; it is closely linked to the latter markers. From our recent data, this interval represents a genetic distance of approximately 10 cM. In the present study, we have studied 14 French families with X-linked juvenile RS by using four CA polymorphisms that are closely linked to the RS locus and that have recently been included in an Xp22.1-p22.2 high-resolution map. Complete cosegregation with the disease locus was observed for three of them, DXS207, DXS418, and DXS999, which further confirms the locus homogeneity for RS and the close linkage to this region. One recombinant was found with the most proximal marker, AFM291wf5, thereby defining this marker as the new proximal boundary of the candidate region for RS. Under the assumption that DXS207 and DXS43 constitute the distal boundary, the present study further reduces the region containing the disease gene to a interval of 3–4 cM. The results reported here should facilitate the eventual cloning of the RS gene. 相似文献