全文获取类型
收费全文 | 5337篇 |
免费 | 358篇 |
出版年
2023年 | 19篇 |
2022年 | 38篇 |
2021年 | 101篇 |
2020年 | 46篇 |
2019年 | 82篇 |
2018年 | 120篇 |
2017年 | 94篇 |
2016年 | 153篇 |
2015年 | 224篇 |
2014年 | 275篇 |
2013年 | 420篇 |
2012年 | 456篇 |
2011年 | 443篇 |
2010年 | 277篇 |
2009年 | 207篇 |
2008年 | 346篇 |
2007年 | 342篇 |
2006年 | 323篇 |
2005年 | 318篇 |
2004年 | 283篇 |
2003年 | 233篇 |
2002年 | 245篇 |
2001年 | 55篇 |
2000年 | 46篇 |
1999年 | 55篇 |
1998年 | 51篇 |
1997年 | 37篇 |
1996年 | 44篇 |
1995年 | 39篇 |
1994年 | 32篇 |
1993年 | 42篇 |
1992年 | 28篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 16篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 22篇 |
1983年 | 14篇 |
1982年 | 7篇 |
1981年 | 15篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有5695条查询结果,搜索用时 125 毫秒
971.
Federica Marchesi Lorenzo Piemonti Alberto Mantovani Paola Allavena 《Cytokine & growth factor reviews》2010,21(1):77-82
Invasion and metastasis are key components of cancer progression. Inflammatory mediators, including cytokines and chemokines, can facilitate tumor dissemination. A distinct and largely forgotten path is perineural invasion (PNI), defined as the presence of cancer cells in the perinerium space. PNI is frequently used by many human carcinomas, in particular by pancreas and prostate cancer, and is associated with tumor recurrence and pain in advanced patients. Neurotrophic factors have been identified as molecular determinants of PNI. A role for chemokines in this process has been proposed; the chemokine CX3CL1/Fractalkine attracts receptor positive pancreatic tumor cells to disseminate along peripheral nerves. Better understanding of the neurotropism of malignant cells and of the clinical significance of PNI would help the design of innovative strategies for the control of tumor dissemination and pain in cancer patients. 相似文献
972.
Hydrogen peroxide, nitric oxide and cytosolic ascorbate peroxidase at the crossroad between defence and cell death 总被引:14,自引:0,他引:14
de Pinto MC Paradiso A Leonetti P De Gara L 《The Plant journal : for cell and molecular biology》2006,48(5):784-795
An increase in the production of reactive oxygen species (ROS) is a typical event occurring during different stress conditions and activating conflicting responses in plants. In order to investigate the relevance of different timing and amounts of ROS production, tobacco (Nicotiana tabacum) Bright Yellow-2 (TBY-2) cells were incubated with different amounts of glucose plus glucose oxidase, for generating H(2)O(2) during time, or directly with known amounts of H(2)O(2). Data presented here indicate that, in TBY-2 cells, a difference in H(2)O(2) level is a critical point for shifting metabolic responses towards strengthening of antioxidant defences, or their depletion with consequent cell death. Timing of ROS production is also critical because it can determine programmed cell death (PCD) or necrosis. Depending on the different kinds of activated cell death, ascorbate (ASC) and glutathione (GSH) pools are altered differently. Moreover, an H(2)O(2)-dependent activation of nitric oxide synthesis is triggered only in the conditions inducing PCD. Ascorbate peroxidase (APX) has been analysed under different conditions of H(2)O(2) generation. Under a threshold value of H(2)O(2) overproduction, a transient increase in APX occurs, whereas under conditions inducing cell necrosis, the activity of APX decreases in proportion to cell death without any evident alteration in APX gene expression. Under conditions triggering PCD, the suppression of APX involves both gene expression and alteration of the kinetic characteristics of the enzyme. The changes in ASC, GSH and APX are involved in the signalling pathway leading to PCD, probably contributing to guaranteeing the cellular redox conditions required for successful PCD. 相似文献
973.
Jones P Altamura S Chakravarty PK Cecchetti O De Francesco R Gallinari P Ingenito R Meinke PT Petrocchi A Rowley M Scarpelli R Serafini S Steinkühler C 《Bioorganic & medicinal chemistry letters》2006,16(23):5948-5952
Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates. 相似文献
974.
Pevarello P Fancelli D Vulpetti A Amici R Villa M Pittalà V Vianello P Cameron A Ciomei M Mercurio C Bischoff JR Roletto F Varasi M Brasca MG 《Bioorganic & medicinal chemistry letters》2006,16(4):1084-1090
We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained. 相似文献
975.
976.
977.
The genomic and gene organisation of 5S rDNA clusters have been extensively characterized in bony fish and eukaryotes, providing
general issues for understanding the molecular evolution of this multigene DNA family. By contrast, the 5S rDNA features have
been rarely investigated in cartilaginous fish (only three species). Here, we provide evidence for a dual 5S rDNA gene system
in the Rajidae by sequence analysis of the coding region (5S) and adjacent nontranscribed spacer (NTS) in five Mediterranean
species of rays (Rajidae), and in a large number of piscine taxa including lampreys and bony fish. As documented in several
bony fish, two functional 5S rDNA types were found here also in the rajid genome: a short one (I) and a long one (II), distinguished
by distinct 5S and NTS sequences. That the ancestral piscine genome had these two 5S rDNA loci might be argued from the occurrence
of homologous dual gene systems that exist in several fish taxa and from 5S phylogenetic relationships. An extensive analysis
of NTS-II sequences of Rajidae and Dasyatidae revealed the occurrence of large simple sequence repeat (SSR) regions that are
formed by microsatellite arrays. The localization and organization of SSR within the NTS-II are conserved in Rajiformes since
the Upper Cretaceous. The direct correlation between the SSRs extension and the NTS length indicated that they might play
a role in the maintenance of the larger 5S rDNA clusters in rays. The phylogenetic analysis indicated that NTS-II is a valuable
systematic tool limited to distantly related taxa of Rajiformes.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
[Reviewing Editor: Dr. Rafael Zardoya] 相似文献
978.
979.
980.
Agnès Fleury Jael Moreno García Paulina Valdez Aguerrebere María de Sayve Durán Paola Becerril Rodríguez Carlos Larralde Edda Sciutto 《PLoS neglected tropical diseases》2010,4(8)