全文获取类型
收费全文 | 7010篇 |
免费 | 610篇 |
国内免费 | 4篇 |
出版年
2023年 | 64篇 |
2022年 | 117篇 |
2021年 | 250篇 |
2020年 | 117篇 |
2019年 | 180篇 |
2018年 | 156篇 |
2017年 | 141篇 |
2016年 | 211篇 |
2015年 | 394篇 |
2014年 | 364篇 |
2013年 | 452篇 |
2012年 | 518篇 |
2011年 | 469篇 |
2010年 | 309篇 |
2009年 | 296篇 |
2008年 | 352篇 |
2007年 | 355篇 |
2006年 | 318篇 |
2005年 | 281篇 |
2004年 | 244篇 |
2003年 | 249篇 |
2002年 | 235篇 |
2001年 | 74篇 |
2000年 | 63篇 |
1999年 | 82篇 |
1998年 | 58篇 |
1997年 | 49篇 |
1996年 | 47篇 |
1995年 | 36篇 |
1994年 | 40篇 |
1993年 | 45篇 |
1992年 | 48篇 |
1991年 | 58篇 |
1990年 | 46篇 |
1989年 | 41篇 |
1988年 | 42篇 |
1987年 | 48篇 |
1986年 | 38篇 |
1985年 | 35篇 |
1984年 | 54篇 |
1983年 | 34篇 |
1982年 | 39篇 |
1980年 | 31篇 |
1979年 | 47篇 |
1978年 | 35篇 |
1977年 | 41篇 |
1976年 | 41篇 |
1975年 | 49篇 |
1974年 | 28篇 |
1972年 | 31篇 |
排序方式: 共有7624条查询结果,搜索用时 31 毫秒
951.
Adir Y Welch LC Dumasius V Factor P Sznajder JI Ridge KM 《American journal of physiology. Lung cellular and molecular physiology》2008,294(6):L1233-L1237
Mechanical ventilation with high tidal volumes (HV(T)) impairs lung liquid clearance (LLC) and downregulates alveolar epithelial Na-K-ATPase. We have previously reported that the Na-K-ATPase alpha(2)-subunit contributes to LLC in normal rat lungs. Here we tested whether overexpression of Na-K-ATPase alpha(2)-subunit in the alveolar epithelium would increase clearance in a HV(T) model of lung injury. We infected rat lungs with a replication-incompetent adenovirus that expresses Na-K-ATPase alpha(2)-subunit gene (Adalpha(2)) 7 days before HV(T) mechanical ventilation. HV(T) ventilation decreased LLC by approximately 50% in untreated, sham, and Adnull-infected rats. Overexpression of Na-K-ATPase alpha(2)-subunit prevented the decrease in clearance caused by HV(T) and was associated with significant increases in Na-K-ATPase alpha(2) protein abundance and activity in peripheral lung basolateral membrane fractions. Ouabain at 10(-5) M, a concentration that inhibits the alpha(2) but not the Na-K-ATPase alpha(1), decreased LLC in Adalpha(2)-infected rats to the same level as sham and Adnull-infected lungs, suggesting that the increased clearance in Adalpha(2) lungs was due to Na-K-ATPase alpha(2) expression and activity. In summary, we provide evidence that augmentation of the Na-K-ATPase alpha(2)-subunit, via gene transfer, may accelerate LLC in the injured lung. 相似文献
952.
The oxidation of the hexacarbonyl(1,3-dithiolato-S,S')diiron complexes 4a-4c with varying amounts of dimethyldioxirane (DMD) was systematically studied. The chemoselectivity of the oxidation products depended upon the substituent R (R=H, Me, 1/2 (CH2)(5)). For R=H, four oxidation products, 6a-6d, have been obtained. In the case of R=Me, three products, 7a-7c, were formed, and for R=1/2 (CH2)(5), only complex 8 was observed. These observations are due to steric and electronic effects caused by the substituent R. Additionally, oxidation of the triiron complex 5 with DMD was performed to yield the products 9a and 9b. X-Ray diffraction analyses were performed for 6a-6d, 7a, and 7c, as well as for 9a and 9b. The electronic properties were determined by density-functional theory (DFT) calculations. 相似文献
953.
954.
Flow is an open source software application for clinical and experimental researchers to perform exploratory data analysis, clustering and annotation of flow cytometric data. Flow is an extensible system that offers the ease of use commonly found in commercial flow cytometry software packages and the statistical power of academic packages like the R BioConductor project. 相似文献
955.
The obligate intracellular bacterial pathogen Chlamydia trachomatis replicates within a large vacuole or "inclusion" that expands as bacteria multiply but is maintained as an intact organelle. Here, we report that the inclusion is encased in a scaffold of host cytoskeletal structures made up of a network of F-actin and intermediate filaments (IF) that act cooperatively to stabilize the pathogen-containing vacuole. Formation of F-actin at the inclusion was dependent on RhoA, and its disruption led to the disassembly of IFs, loss of inclusion integrity, and leakage of inclusion contents into the host cytoplasm. In addition, IF proteins were processed by the secreted chlamydial protease CPAF to form filamentous structures at the inclusion surface with altered structural properties. We propose that Chlamydia has co-opted the function of F-actin and IFs to stabilize the inclusion with a dynamic, structural scaffold while minimizing the exposure of inclusion contents to cytoplasmic innate immune-surveillance pathways. 相似文献
956.
Arash Rafii Pejman Mirshahi Mary Poupot Anne-Marie Faussat Anne Simon Elodie Ducros Eliane Mery Bettina Couderc Raphael Lis Jerome Capdet Julie Bergalet Denis Querleu Francoise Dagonnet Jean-Jacques Fournié Jean-Pierre Marie Eric Pujade-Lauraine Gilles Favre Jeanine Soria Massoud Mirshahi 《PloS one》2008,3(12)
Background
The microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.Methodology/Principal Findings
We isolated an original type of stromal cells, referred to as “Hospicells” from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.Conclusions/Significance
This is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient''s tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy. 相似文献957.
Jacob DA Ray T Bengston CL Lindsten T Wu J Thompson CB Forger NG 《Developmental neurobiology》2008,68(11):1303-1314
The bulbocavernosus (BC) and levator ani (LA) muscles are present in males but absent or severely reduced in females, and the fate of these muscles controls the survival of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus. However, the mechanism underlying the sex difference in BC and LA development has been controversial. We examined the role of cell death in sexual differentiation of the bulbocavernosus BC/LA muscles in mice. Muscle development was mapped from embryonic day 16 (E16) to postnatal day 5 (P5). A sex difference (male>female) first arose on E17 (BC) or E18 (LA), and increased in magnitude postnatally. TUNEL labeling revealed dying cells in the BC and LA muscles of both sexes perinatally. However, females had a significantly higher density of TUNEL-positive cells than did males. A role for the proapoptotic factors, Bax and Bak, in BC/LA development was tested by examining mice lacking one or both of these proteins. In females lacking either Bax or Bak, the BC was absent and the LA rudimentary. Deletion of both bax and bak genes, however, rescued the BC, increased LA size approximately 20-fold relative to controls, and virtually eliminated TUNEL-positive cells in both muscles. We conclude that cell death plays an essential role in sexual differentiation of the BC/LA muscles. The presence of either Bax or Bak is sufficient for cell death in the BC/LA, whereas the absence of both prevents sexually dimorphic muscle cell death. 相似文献
958.
Nasser MW Datta J Nuovo G Kutay H Motiwala T Majumder S Wang B Suster S Jacob ST Ghoshal K 《The Journal of biological chemistry》2008,283(48):33394-33405
959.
Kalie E Jaitin DA Podoplelova Y Piehler J Schreiber G 《The Journal of biological chemistry》2008,283(47):32925-32936
Type I interferons (IFNs) signal for their diverse biological effects by binding a common receptor on target cells, composed of the two transmembrane IFNAR1 and IFNAR2 proteins. We have previously differentially enhanced the antiproliferative activity of IFN by increasing the weak binding affinity of IFN to IFNAR1. In this study, we further explored the affinity interdependencies between the two receptor subunits and the role of IFNAR1 in differential IFN activity. For this purpose, we generated a panel of mutations targeting the IFNAR2 binding site on the background of the IFNalpha2 YNS mutant, which increases the affinity to IFNAR1 by 60-fold, resulting in IFNAR2-to-IFNAR1 binding affinity ratios ranging from 1000:1 to 1:1000. Both the antiproliferative and antiviral potencies of the interferon mutants clearly correlated to the in situ binding IC(50) values, independently of the relative contributions of the individual receptors, thus relating to the integral lifetime of the complex. However, the antiproliferative potency correlated throughout the entire range of affinities, as well as with prolonged IFNAR1 receptor down-regulation, whereas the antiviral potency reached a maximum at binding affinities equivalent to that of wild-type IFNalpha2. Our data suggest that (i) the specific activity of interferon is related to the ternary complex binding affinity and not to affinity toward individual receptor components and (ii) although the antiviral pathway is strongly dependent on pSTAT1 activity, the cytostatic effect requires additional mechanisms that may involve IFNAR1 down-regulation. This differential interferon response is ultimately mediated through distinct gene expression profiling. 相似文献
960.
UCP2 protects hypothalamic cells from TNF-alpha-induced damage 总被引:1,自引:0,他引:1
Degasperi GR Romanatto T Denis RG Araújo EP Moraes JC Inada NM Vercesi AE Velloso LA 《FEBS letters》2008,582(20):3103-3110
Uncoupling protein 2 (UCP2) is highly expressed in the hypothalamus; however, little is known about the functions it exerts in this part of the brain. Here, we hypothesized that UCP2 protects hypothalamic cells from oxidative and pro-apoptotic damage generated by inflammatory stimuli. Intracerebroventricular injection of tumor necrosis factor alpha (TNF-alpha)-induced an increase of UCP2 expression in the hypothalamus, which was accompanied by increased expression of markers of oxidative stress and pro-apoptotic proteins. The inhibition of UCP2 expression by an antisense oligonucleotide enhanced the damaging effects of TNF-alpha. Conversely, increasing the hypothalamic expression of UCP2 by cold exposure reversed most of the effects of the cytokine. Thus, UCP2 acts as a protective factor against cellular damage induced by an inflammatory stimulus in the hypothalamus. 相似文献