全文获取类型
收费全文 | 1261篇 |
免费 | 95篇 |
专业分类
1356篇 |
出版年
2023年 | 6篇 |
2022年 | 19篇 |
2021年 | 32篇 |
2020年 | 22篇 |
2019年 | 34篇 |
2018年 | 35篇 |
2017年 | 29篇 |
2016年 | 43篇 |
2015年 | 83篇 |
2014年 | 82篇 |
2013年 | 108篇 |
2012年 | 112篇 |
2011年 | 96篇 |
2010年 | 70篇 |
2009年 | 55篇 |
2008年 | 84篇 |
2007年 | 71篇 |
2006年 | 47篇 |
2005年 | 50篇 |
2004年 | 50篇 |
2003年 | 43篇 |
2002年 | 34篇 |
2001年 | 8篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 7篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1944年 | 3篇 |
1936年 | 2篇 |
1925年 | 4篇 |
1924年 | 2篇 |
排序方式: 共有1356条查询结果,搜索用时 11 毫秒
11.
Noora Pet?j?niemi Matti Korhonen Jarkko Kortesmaa Karl Tryggvason Kiyotoshi Sekiguchi Hironobu Fujiwara Lydia Sorokin Lars-Eric Thornell Zenebech Wondimu Daniel Assefa Manuel Patarroyo Ismo Virtanen 《The journal of histochemistry and cytochemistry》2002,50(8):1113-1130
Recent studies suggest important functions for laminin-8 (Ln-8; alpha4beta1gamma1) in vascular and blood cell biology, but its distribution in human tissues has remained elusive. We have raised a monoclonal antibody (MAb) FC10, and by enzyme-linked immunoassay (EIA) and Western blotting techniques we show that it recognizes the human Ln alpha4-chain. Immunoreactivity for the Ln alpha4-chain was localized in tissues of mesodermal origin, such as basement membranes (BMs) of endothelia, adipocytes, and skeletal, smooth, and cardiac muscle cells. In addition, the Ln alpha4-chain was found in regions of some epithelial BMs, including epidermis, salivary glands, pancreas, esophageal and gastric glands, intestinal crypts, and some renal medullary tubules. Developmental differences in the distribution of Ln alpha4-chain were detected in skeletal muscle, walls of vessels, and intestinal crypts. Ln alpha4- and Ln alpha2-chains co-localized in BMs of fetal skeletal muscle cells and in some epithelial BMs, e.g., in gastric glands and acini of pancreas. Cultured human pulmonary artery endothelial (HPAE) cells produced Ln alpha4-chain as M(r) 180,000 and 200,000 doublet and rapidly deposited it to the growth substratum. In cell-free extracellular matrices of human kidney and lung, Ln alpha4-chain was found as M(r) 180,000 protein. 相似文献
12.
Stéphane Pédeboscq Denis Gravier Françoise Casadebaig Geneviève Hou Arnaud Gissot Christophe Rey François Ichas Francesca De Giorgi Lydia Lartigue Jean-Paul Pometan 《Bioorganic & medicinal chemistry》2012,20(22):6724-6731
Monoclonal antibodies (MoAb) and tyrosine kinase inhibitors (TKI) targeting the EGFR (Epidermal Growth Factor Receptor) pathways are currently used in colorectal cancer treatment. Despite the improvement of median overall survival, resistance is observed notably due to KRAS and BRAF gene mutations. We synthesized four series of thienopyrimidines whose scaffold is structurally close to TKI used in clinical practice. We evaluated apoptosis induced by these compounds using flow cytometry on KRAS and BRAF mutated cell lines. Our results confirm that the mutated cell lines (HCT116 and HT29) are more resistant to apoptosis than the non-mutated cell line (Hela). Interestingly, among the 13 compounds tested, three of them (5b, 6b and 6d) and gefitinib exhibited a noteworthy pro-apoptotic effect, especially on mutated cell lines with an IC50 value between 70 and 110 μM. These three compounds seem particularly attractive for the development of novel treatments for colorectal cancer patients harboring EGFR pathway mutations. 相似文献
13.
Dr. phil. nat. Lydia Poska-Teiss 《Cell and tissue research》1933,17(3):347-419
Ohne Zusammenfassung 相似文献
14.
15.
16.
Shevin T. Jacob Patricia B. Pavlinac Lydia Nakiyingi Patrick Banura Jared M. Baeten Karen Morgan Amalia Magaret Yuka Manabe Steven J. Reynolds W. Conrad Liles Anna Wald Moses L. Joloba Harriet Mayanja-Kizza W. Michael Scheld 《PloS one》2013,8(8)
Background
When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.Methods
We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.Results
Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].Conclusions
Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection. 相似文献17.
Ecosystems - Nitrogen (N) from anthropogenic sources has dramatically increased in terrestrial ecosystems globally. Although belowground microbial processes and events that release N into the... 相似文献
18.
Rolf J Motta V Duarte N Lundholm M Berntman E Bergman ML Sorokin L Cardell SL Holmberg D 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(8):4821-4827
The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to NOD pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as important players in disease induction, the role of B cells is not clearly understood. In this study we characterize different subpopulations of B cells and demonstrate that marginal zone (MZ) B cells are expanded 2- to 3-fold in NOD mice compared with nondiabetic C57BL/6 (B6) mice. The NOD MZ B cells displayed a normal surface marker profile and localized to the MZ region in the NOD spleen. Moreover, the MZ B cell population developed early during the ontogeny of NOD mice. By 3 wk of age, around the time when autoreactive T cells are first activated, a significant MZ B cell population of adult phenotype was found in NOD, but not B6, mice. Using an F2(B6 x NOD) cross in a genome-wide scan, we map the control of this trait to a region on chromosome 4 (logarithm of odds score, 4.4) which includes the Idd11 and Idd9 diabetes susceptibility loci, supporting the hypothesis that this B cell trait is related to the development of diabetes in the NOD mouse. 相似文献
19.
Chumanevich AA Causey CP Knuckley BA Jones JE Poudyal D Chumanevich AP Davis T Matesic LE Thompson PR Hofseth LJ 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(6):G929-G938
Inflammatory bowel diseases (IBDs), mainly Crohn's disease and ulcerative colitis, are dynamic, chronic inflammatory conditions that are associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism for regulating IBD. Peptidylarginine deiminases (PADs) catalyze the posttranslational conversion of peptidylarginine to peptidylcitrulline in a calcium-dependent, irreversible reaction and mediate the effects of proinflammatory cytokines. Because PAD levels are elevated in mouse and human colitis, we hypothesized that a novel small-molecule inhibitor of the PADs, i.e., chloramidine (Cl-amidine), could suppress colitis in a dextran sulfate sodium mouse model. Results are consistent with this hypothesis, as demonstrated by the finding that Cl-amidine treatment, both prophylactic and after the onset of disease, reduced the clinical signs and symptoms of colitis, without any indication of toxic side effects. Interestingly, Cl-amidine drives apoptosis of inflammatory cells in vitro and in vivo, providing a mechanism by which Cl-amidine suppresses colitis. In total, these data help validate the PADs as therapeutic targets for the treatment of IBD and further suggest Cl-amidine as a candidate therapy for this disease. 相似文献
20.
Emmanuel Olorunleke Adewuyi Yun Zhao Vishnu Khanal Asa Auta Lydia Babatunde Bulndi 《International breastfeeding journal》2017,12(1):51