全文获取类型
收费全文 | 1040篇 |
免费 | 75篇 |
专业分类
1115篇 |
出版年
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 30篇 |
2020年 | 17篇 |
2019年 | 28篇 |
2018年 | 20篇 |
2017年 | 16篇 |
2016年 | 43篇 |
2015年 | 59篇 |
2014年 | 60篇 |
2013年 | 85篇 |
2012年 | 76篇 |
2011年 | 105篇 |
2010年 | 58篇 |
2009年 | 43篇 |
2008年 | 64篇 |
2007年 | 72篇 |
2006年 | 52篇 |
2005年 | 69篇 |
2004年 | 55篇 |
2003年 | 31篇 |
2002年 | 41篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1115条查询结果,搜索用时 15 毫秒
151.
Dave JK Halldorsdottir VG Eisenbrey JR Raichlen JS Liu JB McDonald ME Dickie K Wang S Leung C Forsberg F 《American journal of physiology. Heart and circulatory physiology》2012,303(1):H126-H132
Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg. 相似文献
152.
Despite the key role of proteolysis in various intensively studied biological processes, such as plant immunity, seed development and abiotic stress responses, our knowledge on the identity of natural protease substrates in plants remains scarce. In the genome of the model plant Arabidopsis thaliana, for instance, approximately 700 genes code for proteases. However, only a few natural substrates have been identified, mainly because of the previous lack of sensitive proteomics technologies enabling the identification of low abundant proteins, together with a delay in the implementation of these technologies in the field of plant research. Here, we review the current knowledge on the identity of natural plant protease substrates and describe recently established degradomics technologies that should allow proteome-wide studies of plant proteases in the near future. 相似文献
153.
van der Tol A Van Biesen W Van Laecke S Bogaerts K De Lombaert K Warrinnier H Vanholder R 《PloS one》2012,7(2):e31639
Background
Microalbuminuria (MAU) is considered as a predictor or marker of cardiovascular and renal events. Statins are widely prescribed to reduce cardiovascular risk and to slow down progression of kidney disease. But statins may also generate tubular MAU. The current observational study evaluated the impact of statin use on the interpretation of MAU as a predictor or marker of cardiovascular or renal disease.Methodology/Principal Findings
We used cross-sectional data of ERICABEL, a cohort with 1,076 hypertensive patients. MAU was defined as albuminuria ≥20 mg/l. A propensity score was created to correct for “bias by indication” to receive a statin. As expected, subjects using statins vs. no statins had more cardiovascular risk factors, pointing to bias by indication. Statin users were more likely to have MAU (OR: 2.01, 95%CI: 1.34–3.01). The association between statin use and MAU remained significant after adjusting for the propensity to receive a statin based on cardiovascular risk factors (OR: 1.82, 95%CI: 1.14–2.91). Next to statin use, only diabetes (OR: 1.92, 95%CI: 1.00–3.66) and smoking (OR: 1.49, 95%CI: 0.99–2.26) were associated with MAU.Conclusions
Use of statins is independently associated with MAU, even after adjusting for bias by indication to receive a statin. In the hypothesis that this MAU is of tubular origin, statin use can result in incorrect labeling of subjects as having a predictor or marker of cardiovascular or renal risk. In addition, statin use affected the association of established cardiovascular risk factors with MAU, blurring the interpretation of multivariable analyses. 相似文献154.
The generation of affinity reagents, usually monoclonal antibodies, remains a critical bottleneck in biomedical research and diagnostic test development. Recombinant antibody-like proteins such as scFv have yet to replace traditional monoclonal antibodies in antigen detection applications, in large part because of poor performance of scFv in solution. To address this limitation, we have developed assays that use whole yeast cells expressing scFv on their surfaces (yeast-scFv) in place of soluble purified scFv or traditional monoclonal antibodies. In this study, a nonimmune library of human scFv displayed on the surfaces of yeast cells was screened for clones that bind to recombinant cyst proteins of Entamoeba histolytica, an enteric pathogen of humans. Selected yeast-scFv clones were stabilized by lyophilization and used in detection assay formats in which the yeast-scFv served as solid support-bound monoclonal antibodies. Specific binding of antigen to the yeast-scFv was detected by staining with rabbit polyclonal antibodies. In flow cytometry-based assays, lyophilized yeast-scFv reagents retained full binding activity and specificity for their cognate antigens after 4 weeks of storage at room temperature in the absence of desiccants or stabilizers. Because flow cytometry is not available to all potential assay users, an immunofluorescence assay was also developed that detects antigen with similar sensitivity and specificity. Antigen-specific whole-cell yeast-scFv reagents can be selected from nonimmune libraries in 2-3 weeks, produced in vast quantities, and packaged in lyophilized form for extended shelf life. Lyophilized yeast-scFv show promise as low cost, renewable alternatives to monoclonal antibodies for diagnosis and research. 相似文献
155.
Protecting confidentiality is an essential value in all human relationships, no less in medical practice and research.(1) Doctor-patient and researcher-participant relationships are built on trust and on the understanding those patients' secrets will not be disclosed.(2) However, this confidentiality can be breached in some situations where it is necessary to meet a strong conflicting duty.(3) Confidentiality, in a general sense, has received much interest in Islamic resources including the Qur'an, Sunnah and juristic writings. However, medical and research confidentiality have not been explored deeply. There are few fatwas about the issue, despite an increased effort by both individuals and Islamic medical organizations to use these institutional fatwas in their research. Infringements on confidentiality make up a significant portion of institutional fatwas, yet they have never been thoroughly investigated. Moreover, the efforts of organizations and authors in this regard still require further exploration, especially on the issue of research confidentiality. In this article, we explore medical and research confidentiality and potential conflicts with this practice as a result of fatwas released by international, regional, and national Islamic Sunni juristic councils. We discuss how these fatwas affect research and publication by Muslim doctors, researchers, and Islamic medical organizations. We argue that more specialized fatwas are needed to clarify Islamic juristic views about medical and research confidentiality, especially the circumstances in which infringements on this confidentiality are justified. 相似文献
156.
Dramatic population increases of the native white ibis in urban areas have resulted in their classification as a nuisance species. In response to community and industry complaints, land managers have attempted to deter the growing population by destroying ibis nests and eggs over the last twenty years. However, our understanding of ibis ecology is poor and a question of particular importance for management is whether ibis show sufficient site fidelity to justify site-level management of nuisance populations. Ibis in non-urban areas have been observed to be highly transient and capable of moving hundreds of kilometres. In urban areas the population has been observed to vary seasonally, but at some sites ibis are always observed and are thought to be behaving as residents. To measure the level of site fidelity, we colour banded 93 adult ibis at an urban park and conducted 3-day surveys each fortnight over one year, then each quarter over four years. From the quarterly data, the first year resighting rate was 89% for females (n = 59) and 76% for males (n = 34); this decreased to 41% of females and 21% of males in the fourth year. Ibis are known to be highly mobile, and 70% of females and 77% of males were observed at additional sites within the surrounding region (up to 50 km distant). Our results indicate that a large proportion of ibis have chosen residency over transience both within the study site and across the broader urban region. Consequently the establishment of refuge breeding habitat should be a priority localised management may be effective at particular sites, but it is likely to have an impact across the broader population. 相似文献
157.
Jack Baker David Bain Jean Clarke Kris French 《Ecological Management & Restoration》2012,13(2):159-165
Summary The Eastern Bristlebird (Dasyornis brachypterus) is an endangered endemic passerine of south‐eastern Australia. The re‐establishment of extirpated populations through translocation was identified as a key action in New South Wales to address the threats to this species associated with habitat fragmentation and widespread and frequent fire. At Jervis Bay during 2003–2005, 50 birds were translocated from Bherwerre Peninsula to Beecroft Peninsula. In the Illawarra in 2008, 50 birds were translocated from Barren Grounds Nature Reserve to Cataract. At Jervis Bay, monitoring indicated that after 7 years, (i) there was no detectable impact on the source population from the removal of birds and (ii) the count at Beecroft Peninsula was 94 birds, with dispersal up to 6.3 km from the release point. In the Illawarra, (i) the source population was recovering 3 years post‐removal and (ii) the maximum count at Cataract was 15 birds after 3.5 years, including evidence of breeding, and after 3 years, the maximum dispersal was 7 km from the release point. Both translocations adhered to five key principles as follows. (i) Feasibility analysis prior to each project was favourable. (ii) For 17 pre‐stated criteria for success, 14 and 10, respectively, were met for Jervis Bay and Illawarra. (iii) Financial accountability was achieved with detailed statements showing budgets of $201k and $92k, respectively, for Jervis Bay and Illawarra. (iv) Ecological research was incorporated into both projects. (v) The results of each project are progressively being published. The re‐introduction at Jervis Bay has succeeded, and we are optimistic about the Illawarra re‐introduction. 相似文献
158.
Carrasco J Van Pel A Neyns B Lethé B Brasseur F Renkvist N van der Bruggen P van Baren N Paulus R Thielemans K Boon T Godelaine D 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(5):3585-3593
We previously characterized the CTL response of a melanoma patient who experienced tumor regression following vaccination with an ALVAC virus coding for a MAGE-A3 Ag. Whereas anti-vaccine CTL were rare in the blood and inside metastases of this patient, anti-tumor CTL recognizing other tumor Ags, mainly MAGE-C2, were 100 times more frequent in the blood and considerably enriched in metastases following vaccination. In this study we report the analysis of the CTL response of a second melanoma patient who showed a mixed tumor response after vaccination with dendritic cells pulsed with two MAGE-A3 antigenic peptides presented, respectively, by HLA-A1 and HLA-DP4. Anti-MAGE-3.A1 CD8 and anti-MAGE-3.DP4 CD4 T cells became detectable in the blood after vaccination at a frequency of approximately 10(-5) among the CD8 or CD4 T cells, respectively, and they were slightly enriched in slowly progressing metastases. Additional anti-tumor CTL were present in the blood at a frequency of 2x10(-4) among the CD8 T cells and, among these, an anti-MAGE-C2 CTL clone was detected only following vaccination and was enriched by >1,000-fold in metastases relative to the blood. The striking similarity of these results with our previous observations further supports the hypothesis that the induction of a few anti-vaccine T cells may prime or restimulate additional anti-tumor T cell clones that are mainly responsible for the tumor regression. 相似文献
159.
Mechnotransduction, the phenomenon by which cells respond to applied force, is necessary for normal cell processes and is implicated in the pathology of several diseases including atherosclerosis. The exact mechanisms which govern how forces can affect gene expression have not been determined, but putative direct force effects on the genome would require transduction through the nuclear lamina. In this study we show that nuclei in cells exposed to shear stress significantly change shape, upregulate nuclear lamins and move lamins from the nuclear interior to the nuclear periphery. We hypothesize that the augmentation of the nuclear lamina at the nuclear periphery protects the nuclear interior from the force and allows a nuclear adaptation to shear stress. We also investigate the shear stress response of nuclei in cells that have been transfected with lamin A Delta50, which significantly stiffens nuclei. Lamin A Delta50 causes the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS) and models many aspects of normal aging. We find that the presence of lamin A Delta50 in only 30% of cells greatly reduces the response of the nuclear lamina in all cells in the flow field. We suggest that cells expressing lamin A Delta50 lack the ability to adapt to flow and may prevent neighboring cells from adapting as well. These results provide insight into the development of cardiovascular disease both in patients with HGPS and in normal aging. 相似文献
160.
Milovanova T Chatterjee S Hawkins BJ Hong N Sorokina EM Debolt K Moore JS Madesh M Fisher AB 《Biochimica et biophysica acta》2008,1783(10):1866-1875
Abrupt cessation of flow representing the acute loss of shear stress (simulated ischemia) to flow-adapted pulmonary microvascular endothelial cells (PMVEC) leads to reactive oxygen species (ROS) generation that signals for EC proliferation. We evaluated the role of caveolin-1 on this cellular response with mouse PMVEC that were preconditioned for 72 h to laminar flow at 5 dyn/cm(2) followed by stop of flow ("ischemia"). Preconditioning resulted in a 2.7-fold increase in cellular expression of K(ATP) (K(IR) 6.2) channels but no change in expression level of caveolin-1, gp91(phox), or MAP kinases. The initial response to ischemia in wild type cells was cell membrane depolarization that was abolished by gene targeting of K(IR) 6.2. The subsequent response was increased ROS production associated with activation of NADPH oxidase (NOX2) and then phosphorylation of MAP kinases (Erk, JNK). After 24 h of ischemia in wild type cells, the cell proliferation index increased 2.5 fold and the % of cells in S+G(2)/M phases increased 6-fold. This signaling cascade (cell membrane depolarization, ROS production, MAP kinase activation and cell proliferation) was abrogated in caveolin-1 null PMVEC or by treatment of wild type cells with filipin. These studies indicate that caveolin-1 functions as a shear sensor in flow-adapted EC resulting in ROS-mediated cell signaling and endothelial cell proliferation following the abrupt reduction in flow. 相似文献