全文获取类型
收费全文 | 7805篇 |
免费 | 545篇 |
国内免费 | 2篇 |
专业分类
8352篇 |
出版年
2023年 | 46篇 |
2022年 | 80篇 |
2021年 | 142篇 |
2020年 | 84篇 |
2019年 | 115篇 |
2018年 | 140篇 |
2017年 | 135篇 |
2016年 | 236篇 |
2015年 | 385篇 |
2014年 | 437篇 |
2013年 | 487篇 |
2012年 | 719篇 |
2011年 | 689篇 |
2010年 | 443篇 |
2009年 | 410篇 |
2008年 | 570篇 |
2007年 | 473篇 |
2006年 | 461篇 |
2005年 | 370篇 |
2004年 | 393篇 |
2003年 | 370篇 |
2002年 | 344篇 |
2001年 | 53篇 |
2000年 | 44篇 |
1999年 | 56篇 |
1998年 | 76篇 |
1997年 | 55篇 |
1996年 | 59篇 |
1995年 | 40篇 |
1994年 | 35篇 |
1993年 | 48篇 |
1992年 | 26篇 |
1991年 | 21篇 |
1990年 | 19篇 |
1989年 | 24篇 |
1988年 | 17篇 |
1987年 | 18篇 |
1986年 | 18篇 |
1985年 | 14篇 |
1984年 | 19篇 |
1983年 | 31篇 |
1982年 | 20篇 |
1981年 | 17篇 |
1980年 | 12篇 |
1978年 | 9篇 |
1977年 | 12篇 |
1976年 | 10篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1972年 | 6篇 |
排序方式: 共有8352条查询结果,搜索用时 9 毫秒
251.
Christina Nieuwoudt Samantha J. Jones Angela Brooks-Wilson Jinko Graham 《Source code for biology and medicine》2018,13(1):2
Background
Studies that ascertain families containing multiple relatives affected by disease can be useful for identification of causal, rare variants from next-generation sequencing data.Results
We present the R package SimRVPedigree, which allows researchers to simulate pedigrees ascertained on the basis of multiple, affected relatives. By incorporating the ascertainment process in the simulation, SimRVPedigree allows researchers to better understand the within-family patterns of relationship amongst affected individuals and ages of disease onset.Conclusions
Through simulation, we show that affected members of a family segregating a rare disease variant tend to be more numerous and cluster in relationships more closely than those for sporadic disease. We also show that the family ascertainment process can lead to apparent anticipation in the age of onset. Finally, we use simulation to gain insight into the limit on the proportion of ascertained families segregating a causal variant. SimRVPedigree should be useful to investigators seeking insight into the family-based study design through simulation.252.
253.
254.
Activation of MAPK homologues by elicitors in tobacco cells 总被引:17,自引:3,他引:17
Angela Lebrun-Garcia Fatma Ouaked Annick Chiltz Alain Pugin 《The Plant journal : for cell and molecular biology》1998,15(6):773-781
Elicitors of plant defence reactions (such as cryptogein, an elicitin produced by Phytophthora cryptogea , or oligogalacturonides (OGs)), induced in tobacco cell suspensions ( Nicotiana tabacum var Xanthi) a rapid and transient activation of two protein kinases (PKs) with apparent molecular masses of 50 and 46 kDa, respectively. These PKs activated and phosphorylated at tyrosine residues, phosphorylated myelin basic protein (MBP) at serine/threonine residues. Both are recognized by anti-MAPK antibodies. The two MBP kinases possessed the same kinetics of activation, and their activation depended, to the same extent, on different exogenously applied compounds (staurosporine, lanthanum, EGTA). We demonstrate here that the activation of the MBP kinases is calcium dependent and sensitive to staurosporine, a protein kinase inhibitor which annihilates all known responses of tobacco cells to cryptogein. The activation of MBP kinases appeared to be independent of the production of active oxygen species (AOS) and insensitive to calyculin A, a protein phosphatase type 1 and 2A inhibitor. The activation of MAPKs is discussed in relation to the early responses induced by cryptogein. 相似文献
255.
Norton GR Veliotes DG Osadchii O Woodiwiss AJ Thomas DP 《American journal of physiology. Heart and circulatory physiology》2008,294(1):H372-H378
We explored whether the hypertensive heart is susceptible to myocardial dysfunction in viable noninfarcted tissue post-myocardial infarction (MI), the potential mechanisms thereof, and the impact of these changes on pump function. Six to seven months after the ligation of the left anterior descending coronary artery, left ventricular (LV) myocardial systolic function, as assessed from the percent shortening of the noninfarcted lateral wall segmental length determined over a range of filling pressures (ultrasonic transducers placed in the lateral wall in anaesthetized, open-chest, ventilated rats) and the percent thickening of the posterior wall (echocardiography), was reduced in infarcted spontaneous hypertensive rats (SHR-MI) (P < 0.05) but not in normotensive Wistar-Kyoto (WKY-MI) animals compared with corresponding controls [SHR-sham operations (Sham) and WKY-Sham]. This change in the regional myocardial function in SHR-MI, but not in WKY-MI, occurred despite a similar degree of LV dilatation (increased LV end-diastolic dimensions and volume intercept of the LV end-diastolic pressure-volume relation) in SHR-MI and WKY-MI rats and a lack of difference in LV relative wall thinning, LV wall stress, apoptosis [terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL)], or necrosis (pathological score) between SHR-MI and WKY-MI rats. Although the change in regional myocardial function in the SHR-MI group was not associated with a greater reduction in baseline global LV chamber systolic function [end-systolic elastance (LV E(es)) and endocardial fractional shortening determined in the absence of an adrenergic stimulus], in the presence of an isoproterenol challenge, noninfarct-zone LV systolic myocardial dysfunction manifested in a significant reduction in LV E(es) in SHR-MI compared with WKY-MI and SHR and WKY-Sham rats (P < 0.04). In conclusion, these data suggest that with chronic MI, the hypertensive heart is susceptible to the development of myocardial dysfunction, a change that cannot be attributed to excessive chamber dilatation, apoptosis, or necrosis, but which in turn contributes toward a reduced cardiac adrenergic inotropic reserve. 相似文献
256.
Cheung AM Tile L Lee Y Tomlinson G Hawker G Scher J Hu H Vieth R Thompson L Jamal S Josse R 《PLoS medicine》2008,5(10):e196-12
Background
Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.Methods and Findings
This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.Conclusions
Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#) and Current Controlled Trials ( NCT00150969#ISRCTN61708241) 相似文献257.
Angela S. Barbosa Thaís E. Ferraz-Costa Mauro Semer Bernardo Liberman Carlos A. Moreira-Filho 《Human genetics》1995,95(1):63-66
This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients presented an eunochoid female phenotype with normal external genitalia. At laparotomy, the elder sister was found to have bilateral gonadoblastoma. Cytogenetic studies, which included G and C banding and in situ hybridization, showed that the patients had an apparently normal 46, XY karyotype. PCR analyses revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y chromosome pseudoautosomal boundary region sequence in both patients. The presence of the ZFY sequence was detected by Southern hybridization in the two affected sisters. The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The occurrence of gonadoblastoma is discussed in terms of the genetic factors that may lead to tumor development. 相似文献
258.
Weston WM Freeman AB Haberecht C Hackmiller RC Ma L Nugent P Warr E Pisano MM Greene RM 《Life sciences》2002,71(16):1849-1862
259.
Records AR 《Molecular plant-microbe interactions : MPMI》2011,24(7):751-757
Whether they live in the soil, drift in the ocean, survive in the lungs of human hosts or reside on the surfaces of leaves, all bacteria must cope with an array of environmental stressors. Bacteria have evolved an impressive suite of protein secretion systems that enable their survival in hostile environments and facilitate colonization of eukaryotic hosts. Collectively, gram-negative bacteria produce six distinct secretion systems that deliver proteins to the extracellular milieu or directly into the cytosol of host cells. The type VI secretion system (T6SS) was discovered recently and is encoded in at least one fourth of all sequenced gram-negative bacterial genomes. T6SS proteins are evolutionarily and structurally related to phage proteins, and it is likely that the T6SS apparatus is reminiscent of phage injection machinery. Most studies of T6SS function have been conducted in the context of host-pathogen interactions. However, the totality of data suggests that the T6SS is a versatile tool with roles in virulence, symbiosis, interbacterial interactions, and antipathogenesis. This review gives a brief history of T6SS discovery and an overview of the pathway's predicted structure and function. Special attention is paid to research addressing the T6SS of plant-associated bacteria, including pathogens, symbionts and plant growth-promoting rhizobacteria. 相似文献
260.
Growing crops for bioenergy or biofuels is increasingly viewed as conflicting with food production. However, energy use continues to rise and food production requires fuel inputs, which have increased with intensification. Focussing on the question of food or fuel is thus not helpful. The bigger, more pertinent, challenge is how the increasing demands for food and energy can be met in the future, particularly when water and land availability will be limited. Energy crop production systems differ greatly in environmental impact. The use of high-input food crops for liquid transport fuels (first-generation biofuels) needs to be phased out and replaced by the use of crop residues and low-input perennial crops (second/advanced-generation biofuels) with multiple environmental benefits. More research effort is needed to improve yields of biomass crops grown on lower grade land, and maximum value should be extracted through the exploitation of co-products and integrated biorefinery systems. Policy must continually emphasize the changes needed and tie incentives to improved greenhous gas reduction and environmental performance of biofuels. 相似文献