全文获取类型
收费全文 | 3179篇 |
免费 | 193篇 |
国内免费 | 1篇 |
出版年
2024年 | 3篇 |
2023年 | 23篇 |
2022年 | 44篇 |
2021年 | 110篇 |
2020年 | 86篇 |
2019年 | 80篇 |
2018年 | 115篇 |
2017年 | 77篇 |
2016年 | 123篇 |
2015年 | 201篇 |
2014年 | 213篇 |
2013年 | 259篇 |
2012年 | 310篇 |
2011年 | 279篇 |
2010年 | 192篇 |
2009年 | 164篇 |
2008年 | 168篇 |
2007年 | 159篇 |
2006年 | 146篇 |
2005年 | 141篇 |
2004年 | 117篇 |
2003年 | 96篇 |
2002年 | 87篇 |
2001年 | 21篇 |
2000年 | 26篇 |
1999年 | 10篇 |
1998年 | 22篇 |
1997年 | 13篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1968年 | 3篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1952年 | 1篇 |
排序方式: 共有3373条查询结果,搜索用时 15 毫秒
101.
Felipe Couñago Ana Aurora Díaz Gavela Gemma Sancho Irene Ortiz Francisco José Marcos Manuel Recio Julio Fernández Raquel Cano Mar Jiménez Israel J. Thuissard David Sanz-Rosa Juan Castro Nováis Eduardo Pardo Yolanda Molina Hugo Pérez García Elia del Cerro 《Reports of Practical Oncology and Radiotherapy》2019,24(5):472-480
AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions. 相似文献
102.
Raquel Portela Catarina R. Leal Pedro L. Almeida Rita G. Sobral 《Microbial biotechnology》2019,12(4):586-610
Although several therapeutic approaches are available for wound and burn treatment and much progress has been made in this area, room for improvement still exists, driven by the urgent need of better strategies to accelerate wound healing and recovery, mostly for cases of severe burned patients. Bacterial cellulose (BC) is a biopolymer produced by bacteria with several advantages over vegetal cellulose, such as purity, high porosity, permeability to liquid and gases, elevated water uptake capacity and mechanical robustness. Besides its biocompatibility, BC can be modified in order to acquire antibacterial response and possible local drug delivery features. Due to its intrinsic versatility, BC is the perfect example of a biotechnological response to a clinical problem. In this review, we assess the BC main features and emphasis is given to a specific biomedical application: wound dressings. The production process and the physical–chemical properties that entitle this material to be used as wound dressing namely for burn healing are highlighted. An overview of the most common BC composites and their enhanced properties, in particular physical and biological, is provided, including the different production processes. A particular focus is given to the biochemistry and genetic manipulation of BC. A summary of the current marketed BC-based wound dressing products is presented, and finally, future perspectives for the usage of BC as wound dressing are foreseen. 相似文献
103.
Marcella Willemsen Rugile Linkut Rosalie M. Luiten Tiago R. Matos 《Pigment cell & melanoma research》2019,32(5):612-622
Tissue‐resident memory T (TRM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. TRM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located TRM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive TRM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive TRM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases. 相似文献
104.
Caio Loureiro Salgado Emmanoel Loss Dias Lorenzzo Lyrio Stringari Luciana Polaco Covre Reynaldo Dietze Fausto Edmundo Lima Pereira Herbet Leonel de Matos Guedes Bartira Rossi-Bergmann Daniel Claudio Oliveira Gomes 《Microbes and infection / Institut Pasteur》2019,21(7):328-335
The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4+ and CD8+ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis. 相似文献
105.
106.
Francielly Cristina Machado Renata Prandini Adum de Matos Fernando Lucas Primo Antonio Claudio Tedesco Paula Rahal Marília Freitas Calmon 《Bioorganic & medicinal chemistry》2019,27(9):1882-1890
Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. The empty nanoemulsion fulfils all necessary requirements to be an excellent DDS. Furthermore, the use of curcumin-nanoemulsion in photodynamic therapy resulted in a high phototoxic effect after activation at 440?nm, decreasing to <10% viable tumor cells after two irradiations and increasing the reactive oxygen species (ROS) production. The use of curcumin-nanoemulsion associated with photodynamic therapy resulted in an increase in the levels of caspase 3/7 activity for the studied MCF-7 cell model, indicating that this therapy triggers a cascade of events that lead to cell death, such as cellular apoptosis. In conclusion, curcumin-nanoemulsion proved to be efficient as a photosensitizing agent, had phototoxic effects, significantly decreased the proliferation of MCF-7 cells and stimulating the ROS production in combination with photodynamic therapy, so, this formulation has a great potential for use in treatment of breast cancer. 相似文献
107.
Marcelo F. da Silva Diehgo T. da Silva Elane G. Giese Igor G. Hamoy Edilson R. Matos 《The Journal of eukaryotic microbiology》2019,66(4):608-616
The coccidians of the family Calyptosporidae are parasites of the tissue and organs of fish and aquatic invertebrates, in particular in the tropical region. In contrast with other apicomplexans of the suborder Eimeriorina, the diversity and ecology of the species of the genus Calyptospora have been poorly investigated, resulting in a lacuna that restricts the understanding of the distribution and prevalence of this group of eukaryote microparasites in the Amazon region. In the present study, the integrated comparative analysis of morphological characteristics, histological and structural traits, and the sequences of a fragment of the 18S rRNA gene, provides support for the identification of a new species of Calyptospora, found parasitizing the hepatic tissue of the piscivorous blue peacock bass, Cichla piquiti, captured in the reservoir of the Estreito hydroelectric dam on the middle Tocantins River in northern Brazil. This new species was named Calyptospora paranaidji n. sp. 相似文献
108.
Dodonov Pavel Harper Karen A. de Oliveira Xavier Rafael Silva Matos Dalva M. 《Plant Ecology》2019,220(7-8):741-756
Plant Ecology - Invasive grasses are an important threat in tropical savannas and grasslands and may be affected by natural and anthropogenic features of the environment. They may affect native... 相似文献
109.
Denise P. Silva Gustavo Duarte Helena D.M. Villela Henrique F. Santos Phillipe M. Rosado Joo Gabriel Rosado Alexandre S. Rosado Edir M. Ferreira Adriana U. Soriano Raquel S. Peixoto 《Ecology and evolution》2019,9(9):5172-5185
Although numerous studies have been carried out on the impacts of oil spills on coral physiology, most have relied on laboratory assays. This scarcity is partly explained by the difficulty of reproducing realistic conditions in a laboratory setting or of performing experiments with toxic compounds in the field. Mesocosm systems provide the opportunity to carry out such studies with safe handling of contaminants while reproducing natural conditions required by living organisms. The mesocosm design is crucial and can lead to the development of innovative technologies to mitigate environmental impacts. Therefore, this study aimed to develop a mesocosm system for studies simulating oil spills with several key advantages, including true replication and the use of gravity to control flow‐through that reduces reliance on pumps that can clog thereby decreasing errors and costs. This adaptable system can be configured to (a) have continuous flow‐through; (b) operate as an open or closed system; (c) be fed by gravity; (d) have separate mesocosm sections that can be used for individual and simultaneous experiments; and (e) simulate the migration of oil from ocean oil spills to the nearby reefs. The mesocosm performance was assessed with two experiments using the hydrocoral Millepora alcicornis and different configurations to simulate two magnitudes of oil spills. With few exceptions, physical and chemical parameters remained stable within replicates and within treatments throughout the experiments. Physical and chemical parameters that expressed change during the experiment were still within the range of natural conditions observed in Brazilian marine environments. The photosynthetic potential (Fv/Fm) of the algae associated with M. alcicornis decreased in response to an 1% crude‐oil contamination, suggesting a successful delivery of the toxic contaminant to the targeted replicates. This mesocosm is customizable and adjustable for several types of experiments and proved to be effective for studies of oil spills. 相似文献
110.
Chavarría T Valenciano AI Mayordomo R Egea J Comella JX Hallböök F de Pablo F de la Rosa EJ 《Developmental neurobiology》2007,67(13):1777-1788
Programmed cell death is a genuine developmental process of the nervous system, affecting not only projecting neurons but also proliferative neuroepithelial cells and young neuroblasts. The embryonic chick retina has been employed to correlate in vivo and in vitro studies on cell death regulation. We characterize here the role of two major signaling pathways, PI3K-Akt and MEK-ERK, in controlled retinal organotypic cultures from embryonic day 5 (E5) and E9, when cell death preferentially affects proliferating neuroepithelial cells and ganglion cell neurons, respectively. The relative density of programmed cell death in vivo was much higher in the proliferative and early neurogenic stages of retinal development (E3-E5) than during neuronal maturation and synaptogenesis (E8-E19). In organotypic cultures from E5 and E9 retinas, insulin, as the only growth factor added, was able to completely prevent cell death induced by growth factor deprivation. Insulin activated both the PI3K-Akt and the MEK-ERK pathways. Insulin survival effect, however, was differentially blocked at the two stages. At E5, the effect was blocked by MEK inhibitors, whereas at E9 it was blocked by PI3K inhibitors. The cells which were found to be dependent on insulin activation of the MEK-ERK pathway at E5 were mostly proliferative neuroepithelial cells. These observations support a remarkable specificity in the regulation of early neural cell death. 相似文献