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131.
Kate Bramham Carlos E. Poli-de-Figueiredo Paul T. Seed Annette L. Briley Lucilla Poston Andrew H. Shennan Lucy C. Chappell 《PloS one》2013,8(10)
Objectives
To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ≥500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.Design
Secondary analysis of the Vitamins in Pre-Eclampsia Trial.Setting
25 UK hospitals in ten geographical areas.Population
946 women with pre-existing risk factors for pre-eclampsia.Methods
Women with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ≥500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110).Main Outcome Measures
Maternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5th centile, gestation at delivery.Results
Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P≤0.001), and later in CHT (38.3w; P≤0.05) and GH (39.1w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05).Conclusion
Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500. 相似文献132.
Eva C. Schulte Immanuel Stahl Darina Czamara Daniel C. Ellwanger Sebastian Eck Elisabeth Graf Brit Mollenhauer Alexander Zimprich Peter Lichtner Dietrich Haubenberger Walter Pirker Thomas Brücke Benjamin Bereznai Maria J. Molnar Annette Peters Christian Gieger Bertram Müller-Myhsok Claudia Trenkwalder Juliane Winkelmann 《PloS one》2013,8(11)
Approximately 20% of individuals with Parkinson’s disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance. 相似文献
133.
Chun-Yip Yeung Annette Wai-Kwan Tso Aimin Xu Yu Wang Yu-Cho Woo Tai-Hing Lam Su-Vui Lo Carol Ho-Yee Fong Nelson Ming-Sang Wat Jean Woo Bernard Man-Yung Cheung Karen Siu-Ling Lam 《PloS one》2013,8(10)
Background
Cytokines released from adipose tissues induce chronic low-grade inflammation, which may enhance cancer development. We investigated whether indices of obesity and circulating adipokine levels could predict incident cancer risk.Materials and Methods
This longitudinal community-based study included subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) study commenced in 1995-1996 (CRISP-1) with baseline assessments including indices of obesity. Subjects were reassessed in 2000-2004 (CRISPS-2) with measurement of serum levels of adipokines including interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR2; as a surrogate marker of tumor necrosis factor-α activity), leptin, lipocalin 2, adiponectin and adipocyte-fatty acid binding protein (A-FABP). Incident cancer cases were identified up to 31 December 2011.Results
205 of 2893 subjects recruited at CRISPS-1 had developed incident cancers. More of the subjects who developed cancers were obese (22.1 vs 16.1%) or had central obesity (36.6 vs 24.5%) according to Asian cut-offs. Waist circumference (adjusted HR 1.02 [1.00-1.03] per cm; p=0.013), but not body mass index (adjusted HR 1.04 [1.00-1.08] per kg/m2; p=0.063), was a significant independent predictor for incident cancers after adjustment for age, sex and smoking status. 99 of 1899 subjects reassessed at CRISPS-2 had developed cancers. Subjects who developed cancers had significantly higher level of hsCRP, IL-6, sTNFR2 and lipocalin 2. After adjustment for conventional risk factors, only IL-6 (HR 1.51, 95% CI 1.18-1.95) and sTNFR2 (HR 3.27, 95%CI 1.65-6.47) predicted cancer development.Conclusions
Our data supported the increased risk of malignancy by chronic low grade inflammation related to central obesity. 相似文献134.
Andreas Ziegler Bernd Walz 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1989,165(5):697-709
Summary Superfused slices of drone retina were used for a quantitative analysis of light-induced changes in extracellular Ca2+ concentration ([Ca2+]o) and extracellular space (ECS) volume. 20-ms light flashes elicited biphasic changes in [Ca2+]o. For a saturating flash a brief, initial decrease was followed by a transient increase of 120±34 M. Long, dim steps of light (5 min) produced either a decrease or an increase in [Ca2+]o depending strongly on the previous illumination. Brighter continuous lights caused the [Ca2+]o to increase transiently by 1.4 mM to a peak from which it decayed to a plateau, up to 0.6 mM above the dark concentration.Light flashes (20 ms) caused a shrinkage in ECS volume not exceeding 4%. Thus, changes in [Ca2+]o were almost completely due to Ca2+ fluxes between the ECS and adjacent cells. Continuous lights caused a shrinkage in ECS volume rarely exceeding 16%–20%. Thus, less than 15% of the measured Ca2+ changes could be attributed to shrinkage of the ECS. These data confirm that the ECS functions as a source and a sink for Ca2+ mobilized by light. For comparison, we also made a few measurements of changes in [Ca2+]o in the retina ofCalliphora.Abbreviations [Ca
2+]i
intracellular free Ca2+ concentration
- [Ca
2+]o
extracellular free Ca2+ concentration
-
ECS
extracellular space
-
ER
endoplasmic reticulum
-
TMA
+
tetramethylammonium ion 相似文献
135.
Wenseleers T Van Oystaeyen A 《BioEssays : news and reviews in molecular, cellular and developmental biology》2011,33(12):927-937
The study of alternative genetic systems and mixed modes of reproduction, whereby sexual and asexual reproduction is combined within the same lifecycle, is of fundamental importance as they may shed light on classical evolutionary issues, such as the paradox of sex. Recently, several such cases were discovered in social insects. A closer examination of these systems has revealed many amazing facts, including the mixed use of asexual and sexual reproduction for the production of new queens and workers, males that can clone themselves and the routine use of incest without deleterious genetic consequences. In addition, in several species, remarkable cases of asexually reproducing socially parasitic worker lineages have been discovered. The study of these unusual systems promises to provide insight into many basic evolutionary questions, including the maintenance of sex, the expression of sexual conflict and kin conflict and the evolution of cheating in asexual lineages. 相似文献
136.
Loll B Rückert C Hee CS Saenger W Uchanska-Ziegler B Ziegler A 《Protein science : a publication of the Protein Society》2011,20(2):278-290
The human major histocompatibility complex class I antigen HLA‐B*2705 binds several sequence‐related peptides (pVIPR, RRKWRRWHL; pLPM2, RRRWRRLTV; pGR, RRRWHRWRL). Cross‐reactivity of cytotoxic T cells (CTL) against these HLA‐B*2705:peptide complexes seemed to depend on a particular peptide conformation that is facilitated by the engagement of a crucial residue within the binding groove (Asp116), associated with a noncanonical bulging‐in of the middle portion of the bound peptide. We were interested whether a conformational reorientation of the ligand might contribute to the lack of cross‐reactivity of these CTL with a peptide derived from voltage‐dependent calcium channel α1 subunit (pCAC, SRRWRRWNR), in which the C‐terminal peptide residue pArg9 could engage Asp116. Analyses of the HLA‐B*2705:pCAC complex by X‐ray crystallography at 1.94 Å resolution demonstrated that the peptide had indeed undergone a drastic reorientation, leading it to adopt a canonical binding mode accompanied by the loss of molecular mimicry between pCAC and sequence‐related peptides such as pVIPR, pLMP2, and pGR. This was clearly a consequence of interactions of pArg9 with Asp116 and other F‐pocket residues. Furthermore, we observed an unprecedented reorientation of several additional residues of the HLA‐B*2705 heavy chain near the N‐terminal region of the peptide, including also the presence of double conformations of two glutamate residues, Glu63 and Glu163, on opposing sides of the peptide binding groove. Together with the Arg‐Ser exchange at peptide position 1, there are thus multiple structural reasons that may explain the observed failure of pVIPR‐directed, HLA‐B*2705‐restricted CTL to cross‐react with HLA‐B*2705:pCAC complexes. 相似文献
137.
Wills M Akbar A Beswick M Bosch JA Caruso C Colonna-Romano G Dutta A Franceschi C Fulop T Gkrania-Klotsas E Goronzy J Griffiths SJ Henson S Herndler-Brandstetter D Hill A Kern F Klenerman P Macallan D Macualay R Maier AB Mason G Melzer D Morgan M Moss P Nikolich-Zugich J Pachnio A Riddell N Roberts R Sansoni P Sauce D Sinclair J Solana R Strindhall J Trzonkowski P van Lier R Vescovini R Wang G Westendorp R Pawelec G 《Immunity & ageing : I & A》2011,8(1):10-8
The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion. 相似文献
138.
Continuous loss of CD4(+) T lymphocytes and systemic immune activation are hallmarks of untreated chronic HIV-1 infection. Chronic immune activation during HIV-1 infection is characterized by increased expression of activation markers on T cells, elevated levels of proinflammatory cytokines, and B cell hyperactivation together with hypergammaglobulinemia. Importantly, hyperactivation of T cells is one of the best predictive markers for progression toward AIDS, and it is closely linked to CD4(+) T cell depletion and sustained viral replication. Aberrant activation of T cells is observed mainly for memory CD4(+) and CD8(+) T cells and is documented, in addition to increased expression of surface activation markers, by increased cell cycling and apoptosis. Notably, the majority of these activated T cells are neither HIV specific nor HIV infected, and the antigen specificities of hyperactivated T cells are largely unknown, as are the exact mechanisms driving their activation. B cells are also severely affected by HIV-1 infection, which is manifested by major changes in B cell subpopulations, B cell hyperactivation, and hypergammaglobulinemia. Similar to those of T cells, the mechanisms underlying this aberrant B cell activation remain largely unknown. In this review, we summarized current knowledge about proposed antigen-dependent and -independent mechanisms leading to lymphocyte hyperactivation in the context of HIV-1 infection. 相似文献
139.
Babiychuk EB Atanassoff AP Monastyrskaya K Brandenberger C Studer D Allemann C Draeger A 《PloS one》2011,6(8):e23706
Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1--a member of a family of Ca(2+) and membrane-binding proteins--to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this "kiss-of-death" increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis. 相似文献
140.
Eva Schnabel Stefan Karrasch Holger Schulz Sven Gl?ser Christa Meisinger Margit Heier Annette Peters H-Erich Wichmann Jürgen Behr Rudolf M Huber Joachim Heinrich 《Respiratory research》2011,12(1):50