全文获取类型
收费全文 | 4330篇 |
免费 | 312篇 |
国内免费 | 1篇 |
专业分类
4643篇 |
出版年
2023年 | 18篇 |
2022年 | 39篇 |
2021年 | 106篇 |
2020年 | 63篇 |
2019年 | 81篇 |
2018年 | 107篇 |
2017年 | 90篇 |
2016年 | 145篇 |
2015年 | 193篇 |
2014年 | 225篇 |
2013年 | 257篇 |
2012年 | 403篇 |
2011年 | 353篇 |
2010年 | 234篇 |
2009年 | 176篇 |
2008年 | 259篇 |
2007年 | 274篇 |
2006年 | 269篇 |
2005年 | 197篇 |
2004年 | 225篇 |
2003年 | 207篇 |
2002年 | 189篇 |
2001年 | 32篇 |
2000年 | 30篇 |
1999年 | 45篇 |
1998年 | 54篇 |
1997年 | 44篇 |
1996年 | 29篇 |
1995年 | 41篇 |
1994年 | 25篇 |
1993年 | 17篇 |
1992年 | 21篇 |
1991年 | 22篇 |
1990年 | 28篇 |
1989年 | 13篇 |
1988年 | 16篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 3篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1975年 | 12篇 |
1973年 | 4篇 |
1972年 | 2篇 |
排序方式: 共有4643条查询结果,搜索用时 15 毫秒
71.
Anna Maria Di Giacomo Luana Calabrò Riccardo Danielli Ester Fonsatti Erica Bertocci Isabella Pesce Carolina Fazio Ornella Cutaia Diana Giannarelli Clelia Miracco Maurizio Biagioli Maresa Altomonte Michele Maio 《Cancer immunology, immunotherapy : CII》2013,62(6):1021-1028
Background
Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.Methods
Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4+ and CD8+ T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.Results
Median overall survival among 27 patients was 9.6 months (95 % CI 3.2–16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS+ T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.Conclusions
Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS+ T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required. 相似文献72.
Paolo Bianco Roger Barker Oliver Brüstle Elena Cattaneo Hans Clevers George Q Daley Michele De Luca Lawrence Goldstein Olle Lindvall Christine Mummery Clara Sattler de Sousa e Brito Austin Smith 《The EMBO journal》2013,32(11):1489-1495
At the time of writing, the Italian Parliament is debating a new law that would make it legal to practice an unproven stem cell treatment in public hospitals. The treatment, offered by a private non‐medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulations. This case raises multiple concerns, most prominently the urgent need to protect patients who are severely ill, exposed to significant risks, and vulnerable to exploitation. The scientific community must consider the context—social, financial, medical, legal—in which stem cell science is currently situated and the need for stringent regulation. Additional concerns are emerging. These emanate from the novel climate, created within science itself, and stem cell science in particular, by the currently prevailing model of ‘translational medicine’. Only rigorous science and rigorous regulation can ensure translation of science into effective therapies rather than into ineffective market products, and mark, at the same time, the sharp distinction between the striving for new therapies and the deceit of patients. 相似文献
73.
Claudia C. Cornilescu Gabriel Cornilescu Hongyu Rao Sarah F. Porter Marco Tonelli Michele L. DeRider John L. Markley Fariba M. Assadi‐Porter 《Proteins》2013,81(6):919-925
The sweet protein brazzein, a member of the Csβα fold family, contains four disulfide bonds that lend a high degree of thermal and pH stability to its structure. Nevertheless, a variable temperature study has revealed that the protein undergoes a local, reversible conformational change between 37 and 3°C with a midpoint about 27°C that changes the orientations and side‐chain hydrogen bond partners of Tyr8 and Tyr11. To test the functional significance of this effect, we used NMR saturation transfer to investigate the interaction between brazzein and the amino terminal domain of the sweet receptor subunit T1R2; the results showed a stronger interaction at 7°C than at 37°C. Thus the low temperature conformation, which alters the orientations of two loops known to be critical for the sweetness of brazzein, may represent the bound state of brazzein in the complex with the human sweet receptor. Proteins 2013; © 2012 Wiley Periodicals, Inc. 相似文献
74.
Ira Espuny-Camacho Kimmo A. Michelsen David Gall Daniele Linaro Anja Hasche Jérôme Bonnefont Camilia Bali David Orduz Angéline Bilheu Adèle Herpoel Nelle Lambert Nicolas Gaspard Sophie Péron Serge N. Schiffmann Michele Giugliano Afsaneh Gaillard Pierre Vanderhaeghen 《Neuron》2013,77(3):440-456
Download : Download video (68MB) 相似文献
75.
Michele Lemonnier-Darcemont Anne-Marie Dutrillaux Bernard Dutrillaux Christian Darcemont 《法国昆虫学会纪事》2013,49(3):401-407
Saga rhodiensis se révèle très proche de S. natoliae et ces deux taxons s’acceptent mutuellement pour la copulation. En outre, ils constituent, avec S. hellenica, un groupe assez homogène au niveau chromosomique. Sur le plan morphologique S. hellenica se distingue aisément des deux autres espèces, et aucun accouplement croisé n’a pu aboutir dans nos élevages. La découverte d’individus femelles de S. natoliae présentant les critères morphologiques de S. rhodiensis bien audelà de l’aire de distribution actuellement connue, nous interroge sur la pertinence de ces critères. Des investigations complémentaires sont nécessaires pour préciser le statut exact de S. rhodiensis. 相似文献
76.
77.
Marco Rossi Maria Rita Pitari Nicola Amodio Maria Teresa Di Martino Francesco Conforti Emanuela Leone Cirino Botta Francesco Maria Paolino Teresa Del Giudice Eleonora Iuliano Michele Caraglia Manlio Ferrarini Antonio Giordano Pierosandro Tagliaferri Pierfrancesco Tassone 《Journal of cellular physiology》2013,228(7):1506-1515
78.
Federica Vacondio Caterina Carmi Elena Galvani Michele Bassi Claudia Silva Alessio Lodola Silvia Rivara Andrea Cavazzoni Roberta R. Alfieri Pier Giorgio Petronini Marco Mor 《Bioorganic & medicinal chemistry letters》2013,23(19):5290-5294
In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5–6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. 相似文献
79.
Graziano Di Giuseppe Michele Barbieri Adriana Vallesi Pierangelo Luporini Fernando Dini 《Molecular ecology》2013,22(15):4029-4037
Nuclear (18S and ITS) and mitochondrial (16S) ribosomal RNA gene sequences were determined from genetically distinct wild‐type strains of Antarctic (nine strains), Fuegian (four strains), Greenland (nine strains) and Svalbard (three strains) populations of the marine ciliate, Euplotes nobilii, and analysed for their nucleotide polymorphisms. A close genetic homogeneity was found within and between the Antarctic and Fuegian populations, while more significant levels of genetic differentiation were detected within and between the two Arctic populations, as well as between these populations and the Antarctic/Fuegian ones. The phylogeographical pattern that was derived from these data indicates that gene flow is not limited among Arctic populations; it equally connects the Arctic and Antarctic populations either directly, or through the Fuegian population. This indication reinforces previous evidence from laboratory assays of mating interactions between some of the strains analysed in this work that Southern and Northern polar populations of E. nobilii belong to a unique, panmictic population that substantially share the same gene pool. 相似文献
80.
Cristine Rodrigues Luciana P. S. Vandenberghe Wilerson Sturm Dario E. A. Dergint Michele Rigon Spier Júlio Cesar de Carvalho Carlos R. Soccol 《World journal of microbiology & biotechnology》2013,29(12):2317-2324
Citric acid (CA) is one of the most important products of fermentation in the world. A great variety of agro-industrial residues can be used in solid state fermentation. Aspergillus niger parental strain (CCT 7716) and two strains obtained by mutagenesis (CCT 7717 and CCT 7718) were evaluated in Erlenmeyer flasks and glass columns using citric pulp (CP) as substrate/support, sugarcane molasses and methanol. Best results using glass columns (forced aeration) were found in the fourth day of fermentation: 278.4, 294.9 and 261.1 g CA/kg of dry CP with CCT 7716, CCT 7718 and CCT 7717, respectively. In Erlenmeyer flasks (aeration by diffusion) CA reached 410.7, 446.8 and 492.7 g CA/kg of dry CP with CCT 7716, CCT 7718 and CCT 7717, respectively. The aeration by diffusion improved CA production by the three strains. A data acquisition system specially developed for biotechnological processes analysis was used to perform the respirometric parameters measurement. 相似文献