全文获取类型
收费全文 | 3053篇 |
免费 | 206篇 |
国内免费 | 2篇 |
专业分类
3261篇 |
出版年
2024年 | 2篇 |
2023年 | 24篇 |
2022年 | 43篇 |
2021年 | 91篇 |
2020年 | 55篇 |
2019年 | 59篇 |
2018年 | 95篇 |
2017年 | 62篇 |
2016年 | 115篇 |
2015年 | 164篇 |
2014年 | 160篇 |
2013年 | 226篇 |
2012年 | 278篇 |
2011年 | 254篇 |
2010年 | 169篇 |
2009年 | 139篇 |
2008年 | 226篇 |
2007年 | 178篇 |
2006年 | 191篇 |
2005年 | 131篇 |
2004年 | 127篇 |
2003年 | 126篇 |
2002年 | 116篇 |
2001年 | 22篇 |
2000年 | 9篇 |
1999年 | 22篇 |
1998年 | 14篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 21篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 16篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1974年 | 4篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1961年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有3261条查询结果,搜索用时 15 毫秒
71.
Ewelina Krzywinska Amelie Cornillon Nerea Allende-Vega Dang-Nghiem Vo Celine Rene Zhao-Yang Lu Christine Pasero Daniel Olive Nathalie Fegueux Patrick Ceballos Yosr Hicheri Michal Sobecki Jean-Fran?ois Rossi Guillaume Cartron Martin Villalba 《PloS one》2016,11(4)
The leucocyte-specific phosphatase CD45 is present in two main isoforms: the large CD45RA and the short CD45RO. We have recently shown that distinctive expression of these isoforms distinguishes natural killer (NK) populations. For example, co-expression of both isoforms identifies in vivo the anti tumor NK cells in hematological cancer patients. Here we show that low CD45 expression associates with less mature, CD56bright, NK cells. Most NK cells in healthy human donors are CD45RA+CD45RO-. The CD45RA-RO+ phenotype, CD45RO cells, is extremely uncommon in B or NK cells, in contrast to T cells. However, healthy donors possess CD45RAdimRO- (CD45RAdim cells), which show immature markers and are largely expanded in hematopoietic stem cell transplant patients. Blood borne cancer patients also have more CD45RAdim cells that carry several features of immature NK cells. However, and in opposition to their association to NK cell progenitors, they do not proliferate and show low expression of the transferrin receptor protein 1/CD71, suggesting low metabolic activity. Moreover, CD45RAdim cells properly respond to in vitro encounter with target cells by degranulating or gaining CD69 expression. In summary, they are quiescent NK cells, with low metabolic status that can, however, respond after encounter with target cells. 相似文献
72.
Lilach Moyal Nataly Feldbaum Neta Goldfeiz Ada Rephaeli Abraham Nudelman Michal Weitman Nataly Tarasenko Batia Gorovitz Leah Maron Shiran Yehezkel Iris Amitay-Laish Ido Lubin Emmilia Hodak 《PloS one》2016,11(1)
The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS. 相似文献
73.
Wojciech Barczak Pawel Golusiński Lukasz Luczewski Wiktoria M. Suchorska Michal M. Masternak Wojciech Golusiński 《Biotechnology letters》2016,38(10):1665-1672
Head and neck squamous cell carcinoma is the sixth leading cause of cancer worldwide. The most common risk factors are carcinogens (tobacco, alcohol), and infection of the human papilloma virus. Surgery is still considered as the treatment of choice in case of head and neck cancer, followed by a reconstructive surgery to enhance the quality of life in the patients. However, the widespread use of artificial implants does not provide appropriate physiological activities and often cannot act as a long-term solution for the patients. Here we review the applicability of multiple stem cell types for tissue engineering of cartilage, trachea, vocal folds and nerves for head and neck injuries. The ability of the cells to self-renew and maintain their pluripotency state makes them an attractive tool in tissue engineering. 相似文献
74.
75.
Michal Hlodák Peter Matúš Lucia Kořenková 《International journal of phytoremediation》2016,18(2):195-199
Heavy metal phytotoxicity assessments usually use soluble metal compounds in spiked soils to evaluate metal bioaccumulation, growth inhibition and adverse effects on physiological parameters. However, exampling mercury phytotoxicity for barley (Hordeum vulgare) this paper highlights unsuitability of this experimental approach. Mercury(II) in spiked soils is extremely bioavailable, and there experimentally determined bioaccumulation is significantly higher compared to reported mercury bioaccumulation efficiency from soils collected from mercury-polluted areas. Our results indicate this is not affected by soil sorption capacity, thus soil ageing and formation of more stable mercuric complexes with soil fractions is necessary for reasonable metal phytotoxicity assessments. 相似文献
76.
77.
Michal Mego Ton van Agthoven Paulina Gronesova Michal Chovanec Vera Miskovska Jozef Mardiak Leendert H. J. Looijenga 《Journal of cellular and molecular medicine》2019,23(2):1128-1136
Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin‐based combination chemotherapy. miR‐371a‐3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR‐371a‐3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR‐371a‐3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR‐371a‐3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S – stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression‐free survival (PFS) and overall survival (OS) compared to patients being positive for miR‐371a‐3p (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.09‐0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07‐0.67, P = 0.03 for OS, respectively). Patients negative for miR‐371a‐3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01‐21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01‐27.81, P = 0.008) compared to patients with miR‐371a‐3p positive in both samples (multivariate analyses were non‐significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR‐371a‐3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis. 相似文献
78.
Michal Bijak Alicja Olejnik Bozena Rokita Agnieszka Morel Angela Dziedzic Elzbieta Miller Joanna Saluk‐Bijak 《Journal of cellular and molecular medicine》2019,23(5):3476-3482
Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease. 相似文献
79.
Michael Jakob Rupar Pawel Golusinski Wojciech Golusinski Michal M. Masternak 《Reports of Practical Oncology and Radiotherapy》2019,24(6):544-550
Human Papillomavirus (HPV) remains one of the most commonly contracted sexually transmitted diseases around the world. There are a multitude of HPV types, some of which may never present any symptoms. Others, however, are considered high-risk types, which increase the chance of the person infected to develop cancer. In recent years, the utilization of nanotechnology has allowed researchers to employ and explore the use of nanoparticles in immunotherapies.The new nanoparticle frontier has opened many doors in this area of research as a form of prevention, diagnosis, and treatment in cancers resulting from HPV. This review will provide a brief background of HPV, its relationship to head and neck cancer (HNC) and present some insight into the field of immunotherapeutic nanoparticles. 相似文献
80.
Strunecký Otakar Kopejtka Karel Goecke Franz Tomasch Jürgen Lukavský Jaromír Neori Amir Kahl Silke Pieper Dietmar H. Pilarski Plamen Kaftan David Koblížek Michal 《Extremophiles : life under extreme conditions》2019,23(1):35-48
Extremophiles - Genotypic and morphological diversity of cyanobacteria in the Rupite hot spring (Bulgaria) was investigated by means of optical microscopy, cultivation, single-cell PCR, and 16S... 相似文献