全文获取类型
收费全文 | 9387篇 |
免费 | 686篇 |
国内免费 | 2篇 |
出版年
2023年 | 46篇 |
2022年 | 118篇 |
2021年 | 220篇 |
2020年 | 132篇 |
2019年 | 173篇 |
2018年 | 226篇 |
2017年 | 188篇 |
2016年 | 312篇 |
2015年 | 504篇 |
2014年 | 583篇 |
2013年 | 689篇 |
2012年 | 821篇 |
2011年 | 853篇 |
2010年 | 551篇 |
2009年 | 429篇 |
2008年 | 560篇 |
2007年 | 561篇 |
2006年 | 487篇 |
2005年 | 506篇 |
2004年 | 427篇 |
2003年 | 404篇 |
2002年 | 352篇 |
2001年 | 85篇 |
2000年 | 56篇 |
1999年 | 83篇 |
1998年 | 92篇 |
1997年 | 66篇 |
1996年 | 57篇 |
1995年 | 56篇 |
1994年 | 45篇 |
1993年 | 43篇 |
1992年 | 31篇 |
1991年 | 31篇 |
1990年 | 38篇 |
1989年 | 20篇 |
1988年 | 17篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 14篇 |
1984年 | 15篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 13篇 |
1979年 | 12篇 |
1978年 | 12篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1970年 | 8篇 |
1968年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
972.
Stefanie F. Geiselhardt Stefan Lamm Claudia Gack Klaus Peschke 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(5):369-378
Species of various insect orders possess specialised tarsal adhesive structures covered by a thin liquid film, which is deposited
in the form of footprints. This adhesive liquid has been suggested to be chemically and physiologically related to the epicuticular
lipid layer, which naturally covers the body of insects and acts as the prime barrier to environmental stresses, such as desiccation.
The functional efficiency of the layer, however, is jeopardised by partial melting that may occur at physiological temperatures.
In this study, light microscopic images of elytral prints show that the epicuticular lipid layer of the Colorado potato beetle
Leptinotarsa decemlineata actually is partially liquid and chemical investigations reveal the high similarity of the epicuticular hydrocarbon pattern
and the tarsal liquid. By means of chemical manipulation of the surface hydrocarbon composition of live beetles, the substance
exchange between their tarsal adhesive hairs and the body surface is monitored. Histological sections of L. decemlineata tarsi, furthermore, reveal glandular cells connected to individual adhesive setae and departing from these results, an idea
of a general mechanism of tarsal secretion is developed and discussed in a functional–ecological context. 相似文献
973.
New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy
Vittore Cereda Diane J. Poole Claudia Palena Sudipto Das Tapan K. Bera Cinzia Remondo James L. Gulley Philip M. Arlen Junko Yokokawa Ira Pastan Jeffrey Schlom Kwong Y. Tsang 《Cancer immunology, immunotherapy : CII》2010,59(1):63-71
New gene expressed in prostate (NGEP) is a prostate-specific gene encoding either a small cytoplasmic protein (NGEP-S) or a larger polytopic membrane protein (NGEP-L). NGEP-L expression is detectable only in prostate cancer, benign prostatic hyperplasia and normal prostate. We have identified an HLA-A2 binding NGEP epitope (designated P703) which was used to generate T cell lines from several patients with localized and metastatic prostate cancer. These T cell lines were able to specifically lyse HLA-A2 and NGEP-expressing human tumor cells. NGEP-P703 tetramer binding assays demonstrated that metastatic prostate cancer patients had a higher frequency of NGEP-specific T cells when compared with healthy donors. Moreover, an increased frequency of NGEP-specific T cells was detected in the peripheral blood mononuclear cells of prostate cancer patients post-vaccination with a PSA-based vaccine, further indicating the immunogenicity of NGEP. These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer. 相似文献
974.
Casoni GL Ulivi P Mercatali L Chilosi M Tomassetti S Romagnoli M Ravaglia C Gurioli C Gurioli C Zoli W Silvestrini R Poletti V 《The International journal of biological markers》2010,25(4):229-235
Idiopathic pulmonary fibrosis (IPF) is difficult to diagnose because of numerous interstitial lung diseases with similar symptoms. As serum DNA has proven useful for early lung cancer detection, we aimed to define the relevance of this marker in discriminating IPF from other fibrotic and nonfibrotic/nonmalignant lung diseases. DNA was quantified in 191 subjects: 64 healthy individuals, 58 patients with IPF, 17 patients with nonspecific pulmonary fibrosis (13 idiopathic nonspecific interstitial pneumonia, 4 chronic hypersensitivity pneumonitis), and 52 patients with other diffuse/nonmalignant lung diseases. The median value of free DNA in IPF patients was 61.1 ng/mL (range 7.1-405), which was significantly higher than that of healthy donors (median 6.8, range 2.2-184) (p<0.001) and that of patients with other diffuse/nonmalignant lung diseases (median 28.0, range 4.2-281) (p=0.004). The area under the ROC curve was 0.926 (95% CI 0.879-0.973) when IPF patients were compared with healthy donors, and 0.702 (95% CI 0.609-0.796) when a comparison was made with non-IPF pulmonary diseases. In conclusion, we observed significantly higher levels of free circulating DNA in patients with IPF than in those with other fibrotic or diffuse/nonmalignant lung diseases. 相似文献
975.
Gianfabio Giorgioni Dario Ambrosini Cristian Vesprini Alan Hudson Cinzia Nasuti Antonio Di Stefano Piera Sozio Osele Ciampi Barbara Costa Claudia Martini Antonio Carrieri Giuseppe Carbonara Christoph Enzensperger Maria Pigini 《Bioorganic & medicinal chemistry》2010,18(19):7085-7091
Based on the well known biological versatility of the imidazoline nucleus, we prepared the novel derivatives 3a–k inspired by 2-BFI scaffold to assess imidazoline molecules as D2-like dopamine receptor ligands. Conservative chemical modifications of the lead structure, such as the introduction of an hydroxy group in the aromatic ring alone or associated with N-benzyl substitution, provided partial (3f) or nearly full (3e and 3h) agonists, all endowed with D2-like potency comparable to that of dopamine. 相似文献
976.
Claudia Bello Michele Cea Giovanna Dal Bello Anna Garuti Ilaria Rocco Gabriella Cirmena Eva Moran Aimable Nahimana Michel A. Duchosal Floriana Fruscione Paolo Pronzato Francesco Grossi Franco Patrone Alberto Ballestrero Marc Dupuis Bernard Sordat Alessio Nencioni Pierre Vogel 《Bioorganic & medicinal chemistry》2010,18(9):3320-3334
Novel α-mannosidase inhibitors of the type (2R,3R,4S)-2-({[(1R)-2-hydroxy-1-arylethyl]amino}methyl)pyrrolidine-3,4-diol have been prepared and assayed for their anticancer activities. Compound 30 with the aryl group = 4-trifluoromethylbiphenyl inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival. 相似文献
977.
Pierfrancesco Biagini Claudio Biancalani Alessia Graziano Nicoletta Cesari Maria Paola Giovannoni Agostino Cilibrizzi Vittorio Dal Piaz Claudia Vergelli Letizia Crocetti Maurizio Delcanale Elisabetta Armani Andrea Rizzi Paola Puccini Paola Maria Gallo Daniele Spinabelli Paola Caruso 《Bioorganic & medicinal chemistry》2010,18(10):3506-3517
A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-α release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. 相似文献
978.
979.
Raffaele Saladino Veronica Neri Claudia Crestini Giovanna Costanzo Michele Graciotti Ernesto Di Mauro 《Journal of molecular evolution》2010,71(2):100-110
We describe the one-pot synthesis of a large variety of nucleic acid bases and related compounds from formamide in the presence
of zirconium minerals as catalysts. The major products observed are: purine, 2-hydroxy pyrimidine, 5-hydroxy pyrimidine, isocytosine,
adenine, urea, and carbodiimide. The synthesis of low molecular weight amides and carboxylic acid derivatives (intermediates
of extant metabolism) was also observed: glyoxylamide, glycolic-, lactic-, succinic-, oxalic-, fumaric-, and maleic acids.
As the major problem in the origin of informational polymers is the instability of their precursors, we also investigated
the effects of zirconia minerals on the stability of ribooligonucleotides in formamide and in water. The relevance of these
findings with respect to the origin of informational polymers and primordial metabolism is discussed. 相似文献
980.
Patricia L. Fernandez Fabianno F. Dutra Letícia Alves Rodrigo T. Figueiredo Diego Mour?o-Sa Guilherme B. Fortes Sophie Bergstrand David L?nn Ricardo R. Cevallos Renata M. S. Pereira Ulisses G. Lopes Leonardo H. Travassos Claudia N. Paiva Marcelo T. Bozza 《The Journal of biological chemistry》2010,285(43):32844-32851
Infectious diseases that cause hemolysis are among the most threatening human diseases, because of severity and/or global distribution. In these conditions, hemeproteins and heme are released, but whether heme affects the inflammatory response to microorganism molecules remains to be characterized. Here, we show that heme increased the lethality and cytokine secretion induced by LPS in vivo and enhanced the secretion of cytokines by macrophages stimulated with various agonists of innate immune receptors. Activation of nuclear factor κB (NF-κB) and MAPKs and the generation of reactive oxygen species were essential to the increase in cytokine production induced by heme plus LPS. This synergistic effect of heme and LPS was blocked by a selective inhibitor of spleen tyrosine kinase (Syk) and was abrogated in dendritic cells deficient in Syk. Moreover, inhibition of Syk and the downstream molecules PKC and PI3K reduced the reactive oxygen species generation by heme. Our results highlight a mechanism by which heme amplifies the secretion of cytokines triggered by microbial molecule activation and indicates possible pathways for therapeutic intervention during hemolytic infectious diseases. 相似文献