全文获取类型
收费全文 | 5293篇 |
免费 | 350篇 |
专业分类
5643篇 |
出版年
2024年 | 4篇 |
2023年 | 20篇 |
2022年 | 66篇 |
2021年 | 97篇 |
2020年 | 45篇 |
2019年 | 79篇 |
2018年 | 116篇 |
2017年 | 94篇 |
2016年 | 152篇 |
2015年 | 218篇 |
2014年 | 273篇 |
2013年 | 408篇 |
2012年 | 452篇 |
2011年 | 436篇 |
2010年 | 274篇 |
2009年 | 205篇 |
2008年 | 341篇 |
2007年 | 340篇 |
2006年 | 320篇 |
2005年 | 318篇 |
2004年 | 281篇 |
2003年 | 229篇 |
2002年 | 244篇 |
2001年 | 53篇 |
2000年 | 46篇 |
1999年 | 54篇 |
1998年 | 50篇 |
1997年 | 37篇 |
1996年 | 43篇 |
1995年 | 39篇 |
1994年 | 30篇 |
1993年 | 41篇 |
1992年 | 28篇 |
1991年 | 15篇 |
1990年 | 17篇 |
1989年 | 16篇 |
1988年 | 15篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 21篇 |
1983年 | 14篇 |
1982年 | 6篇 |
1981年 | 15篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有5643条查询结果,搜索用时 15 毫秒
61.
CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers 总被引:1,自引:0,他引:1
Filaci G Fenoglio D Fravega M Ansaldo G Borgonovo G Traverso P Villaggio B Ferrera A Kunkl A Rizzi M Ferrera F Balestra P Ghio M Contini P Setti M Olive D Azzarone B Carmignani G Ravetti JL Torre G Indiveri F 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(7):4323-4334
Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+ CD28- T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+ CD28- T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+ CD25+ T regulatory lymphocytes associate with CD8+ CD28- T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer. 相似文献
62.
63.
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
64.
65.
66.
p53 Modulates Notch Signaling in MCF‐7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1 下载免费PDF全文
Jieun Yun Ingrid Espinoza Antonio Pannuti Damian Romero Luis Martinez Mary Caskey Adina Stanculescu Maurizio Bocchetta Paola Rizzo Vimla Band Hamid Band Hwan Mook Kim Song‐Kyu Park Keon Wook Kang Maria Laura Avantaggiati Christian R. Gomez Todd Golde Barbara Osborne Lucio Miele 《Journal of cellular physiology》2015,230(12):3115-3127
67.
68.
Mohammad Houshmand Teresa Mortera Blanco Paola Circosta Narjes Yazdi Alireza Kazemi Giuseppe Saglio Mahin Nikougoftar Zarif 《World journal of stem cells》2019,11(8):476-490
Bone marrow microenvironment(BMM) is the main sanctuary of leukemic stem cells(LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the close connection between LSCs and the BMM. The elimination of LSCs is of high importance, since they follow cancer stem cell theory as a part of this population. Based on cancer stem cell theory, a cell with stem cell-like features stands at the apex of the hierarchy and produces a heterogeneous population and governs the disease.Secretion of cytokines, chemokines, and extracellular vesicles, whether through autocrine or paracrine mechanisms by activation of downstream signaling pathways in LSCs, favors their persistence and makes the BMM less hospitable for normal stem cells. While all details about the interactions of the BMM and LSCs remain to be elucidated, some clinical trials have been designed to limit these reciprocal interactions to cure leukemia more effectively. In this review, we focus on chronic myeloid leukemia and acute myeloid leukemia LSCs and their milieu in the bone marrow, how to segregate them from the normal compartment, and finally the possible ways to eliminate these cells. 相似文献
69.
Mechanisms transducing the aldosterone secretagogue signal of endothelins in the human adrenal cortex 总被引:1,自引:0,他引:1
Evidence has been provided that the 21-amino acid hypertensive peptide endothelin (ET)-1 exerts a potent secretagogue effect on human adrenocortical zona glomerulosa (ZG), acting through two receptor subtypes, called ET(A) and ET(B), the signaling mechanism(s) of which has (have) not yet been investigated. Collagenase dispersed human ZG cells were obtained from normal adrenals of patients undergoing nephrectomy/adrenalectomy for renal cancer. The selective ET(A)- and ET(B)-receptor activation was obtained by exposing dispersed cells to ET-1 plus the ET(B)-receptor antagonist BQ-788 and to the ET(B)-receptor agonist BQ-3020, respectively. The phospholipase (PL) C inhibitor U-73122 abolished ET(A) receptor-mediated secretory response, but only partially prevented the ET(B) receptor-mediated one. The phosphatidylinositol 3-kinase inhibitor wortmannin, the calmodulin inhibitor W-7 and the protein kinase (PK) C inhibitor calphostin-C significantly blunted the secretory responses ensuing from the activation of both receptor subtypes. When added together, calphostin-C and wortmannin or W-7 abolished ET(A)-mediated secretory response, but only decreased ET(B)-mediated one. The ET(B) receptor-, but not the ET(A) receptor-mediated aldosterone response was partially reversed by the cyclooxygenase (COX) inhibitor indomethacin, which when added together with U-73122 abolished it. ET(A)-receptor activation raised inositol triphosphate (IP(3)) production from dispersed ZG cells, while ET(B)-receptor stimulation enhanced both IP(3) and prostaglandin-E(2) production. Collectively, our findings indicate that ETs stimulate aldosterone secretion from human ZG cells, acting through ET(A) receptors exclusively coupled to PLC/PKC-dependent pathway and ET(B) receptors coupled to both PLC/PKC- and COX-dependent cascades. 相似文献
70.
Carlo Capelli Guglielmo Antonutto Paola Zamparo Massimo Girardis Pietro Enrico di Prampero 《European journal of applied physiology and occupational physiology》1993,66(3):189-195
The mechanical power (Wtot, W·kg–1) developed during ten revolutions of all-out periods of cycle ergometer exercise (4–9 s) was measured every 5–6 min in six subjects from rest or from a baseline of constant aerobic exercise [50%–80% of maximal oxygen uptake (VO2max)] of 20–40 min duration. The oxygen uptake [VO2 (W·kg–1, 1 ml O2 = 20.9 J)] and venous blood lactate concentration ([la]b, mM) were also measured every 15 s and 2 min, respectively. During the first all-out period, Wtot decreased linearly with the intensity of the priming exercise (Wtot = 11.9–0.25·VO2). After the first all-out period (i greater than 5–6 min), and if the exercise intensity was less than 60% VO2max, Wtot, VO2 and [la]b remained constant until the end of the exercise. For exercise intensities greater than 60% VO2max, VO2 and [la]b showed continuous upward drifts and Wtot continued decreasing. Under these conditions, the rate of decrease of Wtot was linearly related to the rate of increase of V [(d Wtot/dt) (W·kg–1·s–1) = 5.0·10–5 –0.20·(d VO2/dt) (W·kg–1·s–1)] and this was linearly related to the rate of increase of [la]b [(d VO2/dt) (W·kg–1·s–1) = 2.310–4 + 5.910–5·(d [la]b/dt) (mM·s–1)]. These findings would suggest that the decrease of Wtot during the first all-out period was due to the decay of phosphocreatine concentration in the exercising muscles occurring at the onset of exercise and the slow drifts of VO2 (upwards) and of Wtot (downwards) during intense exercise at constant Wtot could be attributed to the continuous accumulation of lactate in the blood (and in the working muscles). 相似文献