全文获取类型
收费全文 | 191篇 |
免费 | 15篇 |
国内免费 | 2篇 |
专业分类
208篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 6篇 |
2015年 | 9篇 |
2014年 | 10篇 |
2013年 | 16篇 |
2012年 | 12篇 |
2011年 | 7篇 |
2010年 | 17篇 |
2009年 | 15篇 |
2008年 | 10篇 |
2007年 | 3篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 1篇 |
1999年 | 1篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 3篇 |
1975年 | 1篇 |
1969年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有208条查询结果,搜索用时 8 毫秒
1.
The ATP-binding-cassette transmembrane transporters (ABC transporters)
known from vertebrates belong to four major subfamilies: (1) the P-
glycoproteins (Pgp); (2) the cystic fibrosis transmembrane conductance
regulators (CFTR); (3) the Tap proteins encoded with the major
histocompatibility complex of mammals; and (4) the peroxisomal membrane
proteins. Both Pgp and CFTR have a structure suggesting a past internal
gene duplication; a phylogenetic analysis indicated that these duplications
occurred independently, while an independent tandem gene duplication
occurred in the case of the Tap family. Both the Pgp and Tap proteins show
evidence of relationship to bacterial ABC transporters lacking internal
duplication, and both are significantly more closely related to the HlyB
and MsbA families of transporters from purple bacteria than they are to ABC
transporters from nonpurple bacteria. The simplest hypothesis to explain
this observation is that eukaryotic Pgp and Tap genes are descended from a
mitochondrial gene or genes that were subsequently translocated to the
nuclear genome. The Pgp genes of eukaryotes are characterized by a
remarkable degree of convergent evolution between the ATP-binding cassettes
of their N- terminal and C-terminal halves, whereas no such convergence is
seen between the two halves of CFTR genes or between the duplicated Tap
genes. Exon 13 of the CFTR gene, which encodes a putative regulatory domain
not found in other ABC transporters apart from CFTR, showed high levels of
both synonymous and nonsynonymous difference in comparisons among different
mammalian species, suggesting that this region is a mutational hot spot.
相似文献
2.
3.
X Xiao G Hintermann AL Demanin J Piret 《Journal of industrial microbiology & biotechnology》1996,16(4):261-262
Streptomyces glaucescens is shown to possess -lactamase activity which is inhibitable by clavulanate. This is important in regard to its use as a cloning host for enzymes of \-lactam biosynthesis. 相似文献
4.
Hammes F Broger T Weilenmann HU Vital M Helbing J Bosshart U Huber P Odermatt RP Sonnleitner B 《Cytometry. Part A》2012,81(6):508-516
Accurate and sensitive online detection tools would benefit both fundamental research and practical applications in aquatic microbiology. Here, we describe the development and testing of an online flow cytometer (FCM), with a specific use foreseen in the field of drinking water microbiology. The system incorporated fully automated sampling and fluorescent labeling of bacterial nucleic acids with analysis at 5-min intervals for periods in excess of 24 h. The laboratory scale testing showed sensitive detection (< 5% error) of bacteria over a broad concentration range (1 × 10(3) -1 × 10(6) cells mL(-1) ) and particularly the ability to track both gradual changes and dramatic events in water samples. The system was tested with bacterial pure cultures as well as indigenous microbial communities from natural water samples. Moreover, we demonstrated the possibility of using either a single fluorescent dye (e.g., SYBR Green I) or a combination of two dyes (SYBR Green I and Propidium Iodide), thus broadening the application possibilities of the system. The online FCM approach described herein has considerable potential for routine and continuous monitoring of drinking water, optimization of specific drinking water processes such as biofiltration or disinfection, as well as aquatic microbiology research in general. 相似文献
5.
ERIC S. BONO PATRICK SMOLINSKI AL CASAGRANDA JUNDE XU 《Computer methods in biomechanics and biomedical engineering》2013,16(2):125-131
The Shear-slip Mesh Update Method (SSMUM) is being used in flow simulations involving large but regular displacements of one or more boundaries of the computational domain. We follow up the earlier discussion of the method with notes on practical implementation aspects. In order to establish a benchmark problem for this class of flow problems, we define and report results from a two-dimensional viscous flow around a rotating stirrer in a square chamber. The application potential of the method is demonstrated in the context of biomedical design problem, as we perform an analysis of blood flow in a centrifugal left ventricular assist device, or blood pump, which involves a rotating impeller in a non-axisymmetric housing. 相似文献
6.
7.
João Paulo Oliveira Corrêa Camilo Elber Vital Marcos Vinícius Marques Pinheiro Diego Silva Batista Cleber Witt Saldanha Ana Cláudia Ferreira da Cruz Marcela Morato Notini Débora Márcia Silva Freitas Fábio Murilo DaMatta Wagner Campos Otoni 《In vitro cellular & developmental biology. Plant》2016,52(1):45-55
8.
Wagner D. Vital Heron F. V. Torquato Larissa de Oliveira Passos Jesus Wagner Alves de Souza Judice Maria Fátima das G. F. da Silva Tiago Rodrigues Giselle Zenker Justo Thiago A. M. Veiga Edgar J. Paredes-Gamero 《Journal of cellular biochemistry》2019,120(6):9608-9623
Several molecules extracted from natural products exhibit different biological activities, such as ion channel modulation, activation of signaling pathways, and anti-inflammatory or antitumor activity. In this study, we tested the antitumor ability of natural compounds extracted from the Raputia praetermissa plant. Among the compounds tested, an alkaloid, here called compound S4 (4-Deoxyraputindole C), showed antitumor effects against human tumor lineages. Compound S4 was the most active against Raji, a lymphoma lineage, promoting cell death with characteristics that including membrane permeabilization, dissipation of the mitochondrial potential, increased superoxide production, and lysosomal membrane permeabilization. The use of cell death inhibitors such as Z-VAD-FMK (caspase inhibitor), necrostatin-1 (receptor-interacting serine/threonine-protein kinase 1 inhibitor), E-64 (cysteine peptidases inhibitor), and N-acetyl- L -cysteine (antioxidant) did not decrease compound S4-dependent cell death. Additionally, we tested the effect of cellular activity on adherent human tumor cells. The highest reduction of cellular activity was observed in A549 cells, a lung carcinoma lineage. In this lineage, the effect on the reduction of the cellular activity was due to cell cycle arrest, without plasma membrane permeabilization, loss of the mitochondrial potential or lysosomal membrane permeabilization. Compound S4 was able to inhibit cathepsin B and L by a nonlinear competitive (negative co-operativity) and simple-linear competitive inhibitions, respectively. The potency of inhibition was higher against cathepsin L. Compound S4 promoted cell cycle arrest at G 0 and G 2 phase, and increase the expression of p16 and p21 proteins. In conclusion, compound S4 is an interesting molecule against cancer, promoting cell death in the human lymphoma lineage Raji and cell cycle arrest in the human lung carcinoma lineage A549. 相似文献
9.
Izabela Jardim Rodrigues Pitta Mariana de Andrea Vilas-Boas Hacker Ligia Rocha Andrade Clarissa Neves Spitz Robson Teixeira Vital Anna Maria Sales Sergio Luiz Gomes Antunes Euzenir Nunes Sarno Marcia Rodrigues Jardim 《PLoS neglected tropical diseases》2022,16(1)
IntroductionPure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature.ObjectiveThis paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT).MethodsFifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS.ResultsParesthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT.DiscussionThe classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients. 相似文献
10.
HENRY SILVERMAN BABIKER AHMED SAMAR AJEILET SUMAIA AL‐FADIL SUHAIL AL‐AMAD HADIR EL‐DESSOUKY IBRAHIM EL‐GENDY MOHAMED EL‐GUINDI MUSTAFA EL‐NIMEIRI RANA MUZAFFAR AZZA SALEH 《Developing world bioethics》2010,10(2):70-77
To help ensure the ethical conduct of research, many have recommended educational efforts in research ethics to investigators and members of research ethics committees (RECs). One type of education activity involves multi‐day workshops in research ethics. To be effective, such workshops should contain the appropriate content and teaching techniques geared towards the learning styles of the targeted audiences. To ensure consistency in content and quality, we describe the development of a curriculum guide, core competencies and associated learning objectives and activities to help educators organize research ethics workshops in their respective institutions. The curriculum guide is divided into modular units to enable planners to develop workshops of different lengths and choose content materials that match the needs, abilities, and prior experiences of the target audiences. The content material in the curriculum guide is relevant for audiences in the Middle East, because individuals from the Middle East who participated in a Certificate Program in research ethics selected and developed the training materials (e.g., articles, powerpoint slides, case studies, protocols). Also, many of the activities incorporate active‐learning methods, consisting of group work activities analyzing case studies and reviewing protocols. The development of such a workshop training curriculum guide represents a sustainable educational resource to enhance research ethics capacity in the Middle East. 相似文献