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991.
992.
Sandra Van Lint Sofie Wilgenhof Carlo Heirman Jurgen Corthals Karine Breckpot Aude Bonehill Bart Neyns Kris Thielemans 《Cancer immunology, immunotherapy : CII》2014,63(9):959-967
Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. In this regard, one of the major focuses of cancer immunotherapy has been the design of vaccines promoting strong tumor-specific cytotoxic T lymphocyte responses in cancer patients. Here, dendritic cells (DCs) play a pivotal role as they are regarded as nature’s adjuvant and as such have become the natural agents for antigen delivery in order to finally elicit strong T cell responses (Villadangos and Schnorrer in Nat Rev Immunol 7:543–555, 2007; Melief in Immunity 29:372–383, 2008; Palucka and Banchereau in Nat Rev Cancer 12:265–277, 2012; Vacchelli et al. in Oncoimmunology 2:e25771, 2013; Galluzzi et al. in Oncoimmunology 1:1111–1134, 2012). Therefore, many investigators are actively pursuing the use of DCs as an efficient way of inducing anticancer immune responses. Nowadays, DCs can be generated at a large scale in closed systems, yielding sufficient numbers of cells for clinical application. In addition, with the identification of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, a whole range of strategies using DCs for immunotherapy have been designed and tested in clinical studies. Despite the evidence that DCs loaded with tumor-associated antigens can elicit immune responses in vivo, clinical responses remained disappointingly low. Therefore, optimization of the cellular product and route of administration was urgently needed. Here, we review the path we have followed in the development of TriMixDC-MEL, a potent DC-based cellular therapy, discussing its development as well as further modifications and applications. 相似文献
993.
Nassira Riah Gilles Béna Abdelhamid Djekoun Karine Heulin Philippe de Lajudie Gisèle Laguerre 《Systematic and applied microbiology》2014
The genetic structure of rhizobia nodulating pea and lentil in Algeria, Northern Africa was determined. A total of 237 isolates were obtained from root nodules collected on lentil (Lens culinaris), proteaginous and forage pea (Pisum sativum) growing in two eco-climatic zones, sub-humid and semi-arid, in Eastern Algeria. They were characterised by PCR-restriction fragment length polymorphism (RFLP) of the 16S–23S rRNA intergenic region (IGS), and the nodD-F symbiotic region. The combination of these haplotypes allowed the isolates to be clustered into 26 distinct genotypes, and all isolates were classified as Rhizobium leguminosarum. Symbiotic marker variation (nodD-F) was low but with the predominance of one nod haplotype (g), which had been recovered previously at a high frequency in Europe. Sequence analysis of the IGS further confirmed its high variability in the studied strains. An AMOVA analysis showed highly significant differentiation in the IGS haplotype distribution between populations from both eco-climatic zones. This differentiation was reflected by differences in dominant genotype frequencies. Conversely, no host plant effect was detected. The nodD gene sequence-based phylogeny suggested that symbiotic gene diversity in pea and lentil nodulating rhizobial populations in Algeria was low compared to that reported elsewhere in the world. 相似文献
994.
Susan Costantini Raffaele Raucci Giovanni Colonna Flavia Anna Mercurio Anna Maria Trotta Ringhieri Paola Marilisa Leone Filomena Rossi Carmela Pellegrino Giuseppe Castello Stefania Scala 《Journal of peptide science》2014,20(4):270-278
CXCR4 is a G‐protein‐coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems. CXCL12/CXCR4 axis plays a central role in diseases, such as HIV, cancer, WHIM syndrome, rheumatoid arthritis, pulmonary fibrosis, and lupus and, hence, indicated as putative therapeutic target. Although multiple CXCR4 antagonists have been developed, there is only one marketed drug, plerixafor, indicated for stem cell mobilization in poor mobilizer patients. In this work, we have designed and synthesized two peptides, six and seven residues long, using as template the N‐terminal region of CXCL12; analyzed their conformations by CD, NMR, and molecular dynamics simulations; simulated their complexes with CXCR4 by docking methods; and validated these data by in vitro studies. The results showed that the two peptides are rather flexible in aqueous solution lacking ordered secondary structure elements and present a promising affinity for CXCR4. This affinity is not revealed for CXCR7, indicating a specificity for CXCR4. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
995.
Stéphane L’Haridon Lijing Jiang Karine Alain Morgane Chalopin Ouafae Rouxel Mickaël Beauverger Hongxiu Xu Zongze Shao Mohamed Jebbar 《Extremophiles : life under extreme conditions》2014,18(1):81-88
A novel strictly anaerobic thermophilic heterotrophic bacterium, strain SLHLJ1T, was isolated from a Pacific hydrothermal sediment. Cells were Gram-negative coccobacilli (approximately 1.0 × 0.6 μm) with a toga. It grew at temperatures between 33 and 78 °C (optimum 70 °C). Elemental sulphur and l-cystine stimulated its growth. It contained C16:0, C16:1 ω11c, C18:0 and C18:1 ω9c as major fatty acids (>5 %), 3 phospholipids and 2 glycolipids as polar lipids. Its DNA G+C content was 43.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences placed strain SLHLJ1T within the family Thermotogaceae. The novel isolate was most closely related to Kosmotoga arenicorallina (97.93 % 16S rRNA gene sequence similarity), K. olearia (92.43 %) and K. shengliensis (92.17 %). On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons with its closest relatives, we propose its assignment to a novel species of the genus Kosmotoga. The name Kosmotoga pacifica sp. nov. is proposed with strain SLHLJ1T (=DSM 26965T = JCM 19180T = UBOCC 3254T) as the type species. 相似文献
996.
997.
998.
Manglio Rizzo Juan Bayo Flavia Piccioni Mariana Malvicini Esteban Fiore Estanislao Peixoto Mariana G. García Jorge B. Aquino Ariel Gonzalez Campa?a Gustavo Podestá Marcelo Terres Oscar Andriani Laura Alaniz Guillermo Mazzolini 《PloS one》2014,9(9)
We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated the effects of LMW HA priming on human-tumor-pulsed monocytes-derived dendritic cells (DC/TL) obtained from healthy donors and patients with CRC. LMW HA treatment resulted in an improved maturation state of DC/TL and an enhanced mixed leucocyte reaction activity in vivo. Importantly, pre-conditioning of DC/TL with LMW HA increased their ability to migrate and reduced their attraction to human tumor derived supernatants. These effects were associated with increased CCR7 expression levels in DC. Indeed, a significant increase in migratory response toward CCL21 was observed in LMW HA primed tumor-pulsed monocyte-derived dendritic cells (DC/TL/LMW HA) when compared to LWM HA untreated cells (DC/TL). Moreover, LMW HA priming modulated other mechanisms implicated in DC migration toward lymph nodes such as the metalloproteinase activity. Furthermore, it also resulted in a significant reduction in DC migratory capacity toward tumor supernatant and IL8 in vitro. Consistently, LMW HA dramatically enhanced in vivo DC recruitment to tumor-regional lymph nodes and reduced DC migration toward tumor tissue. This study shows that LMW HA –a poorly immunogenic molecule- represents a promising candidate to improve human DC maturation protocols in the context of DC-based vaccines development, due to its ability to enhance their immunogenic properties as well as their migratory capacity toward lymph nodes instead of tumors. 相似文献
999.
Dystonia is a neurological disorder in which sustained muscle contractions induce twisting and repetitive movements or abnormal posturing. DYT1 early-onset primary dystonia is the most common form of hereditary dystonia and is caused by deletion of a glutamic acid residue (302/303) near the carboxyl-terminus of encoded torsinA. TorsinA is localized primarily within the contiguous lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), and is hypothesized to function as a molecular chaperone and an important regulator of the ER stress-signaling pathway, but how the mutation in torsinA causes disease remains unclear. Multiple lines of evidence suggest that the clinical symptoms of dystonia result from abnormalities in dopamine (DA) signaling, and possibly involving its down-stream effector adenylate cyclase that produces the second messenger cyclic adenosine-3′, 5′-monophosphate (cAMP). Here we find that mutation in torsinA induces ER stress, and inhibits the cyclic adenosine-3′, 5′-monophosphate (cAMP) response to the adenylate cyclase agonist forskolin. Both defective mechanins are corrected by the small molecule 4-phenylbutyrate (4-PBA) that alleviates ER stress. Our results link torsinA, the ER-stress-response, and cAMP-dependent signaling, and suggest 4-PBA could also be used in dystonia treatment. Other pharmacological agents known to modulate the cAMP cascade, and ER stress may also be therapeutic in dystonia patients and can be tested in the models described here, thus supplementing current efforts centered on the dopamine pathway. 相似文献
1000.
Vinícius de Oliveira Ottone Flávio de Castro Magalh?es Fabrício de Paula Núbia Carelli Pereira Avelar Paula Fernandes Aguiar Pamela Fiche da Matta Sampaio Tamiris Campos Duarte Karine Beatriz Costa Tatiane Líliam Araújo Candido Celso Coimbra Fábio Yuzo Nakamura Fabiano Trigueiro Amorim Etel Rocha-Vieira 《PloS one》2014,9(12)