全文获取类型
收费全文 | 7977篇 |
免费 | 672篇 |
国内免费 | 1篇 |
专业分类
8650篇 |
出版年
2023年 | 33篇 |
2022年 | 89篇 |
2021年 | 178篇 |
2020年 | 77篇 |
2019年 | 117篇 |
2018年 | 135篇 |
2017年 | 116篇 |
2016年 | 247篇 |
2015年 | 377篇 |
2014年 | 448篇 |
2013年 | 520篇 |
2012年 | 680篇 |
2011年 | 661篇 |
2010年 | 454篇 |
2009年 | 436篇 |
2008年 | 539篇 |
2007年 | 527篇 |
2006年 | 470篇 |
2005年 | 459篇 |
2004年 | 434篇 |
2003年 | 416篇 |
2002年 | 370篇 |
2001年 | 73篇 |
2000年 | 51篇 |
1999年 | 67篇 |
1998年 | 81篇 |
1997年 | 62篇 |
1996年 | 50篇 |
1995年 | 41篇 |
1994年 | 52篇 |
1993年 | 55篇 |
1992年 | 33篇 |
1991年 | 37篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 26篇 |
1987年 | 17篇 |
1986年 | 17篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 19篇 |
1982年 | 10篇 |
1981年 | 16篇 |
1980年 | 7篇 |
1978年 | 11篇 |
1977年 | 14篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1972年 | 4篇 |
排序方式: 共有8650条查询结果,搜索用时 0 毫秒
991.
Foulds LM Boysen RI Crane M Yang Y Muir JA Smith AI de Kretser DM Hearn MT Hedger MP 《Biology of reproduction》2008,79(3):525-536
The ability of the gametes to escape detection by the immune system is vital to successful human reproduction. Furthermore, the observed capacity of the testis in some species to support tissue grafts without rejection (immunological privilege) indicates that spermatogenic cells are protected by local immunoregulatory mechanisms. One of these mechanisms involves targeting T cells for inactivation and destruction within the testicular environment. Although the fluids of the testis and ovary surrounding the developing gametes contain soluble factors that inhibit T cells, the identity of the molecule(s) responsible for this activity has been unknown. Using a specific T-cell proliferation assay to monitor bioactivity, these molecules were purified from bovine ovarian follicular fluid by methanol extraction and sequential reverse-phase HPLC (RP-HPLC). All purified active fractions coincided with the elution position on RP-HPLC of several small molecules ranging in size from 496 to 522 Da. The same molecules were localized to the immunosuppressive fractions of rat testicular interstitial fluid. The active molecules were identified, using capillary electrophoresis electrospray ionization mass spectroscopy, as lyso-glycerophosphocholines (lyso-GPCs), namely, 1-palmitoyl-sn-glycero-3-phosphocholine, 1-oleoyl-sn-glycero-3-phosphocholine, a 18:2a/lyso-GPC (putatively, 1-linoleoyl-sn-glycero-3-phosphocholine), and a 20:4a/lyso-GPC (putatively, 1-arachidonyl-sn-glycero-3-phosphocholine). Comparison of the bioactivity and mass spectroscopy profiles of two of the purified molecules with their synthetic standards confirmed the identification. These molecules inhibit T-cell proliferation in response to activation and induce apoptosis of these cells in a time- and dose-dependent manner. The emergence of gonadal lyso-GPCs as potential regulators of critical immune events opens up new avenues of inquiry into the origins of autoimmune infertility and more generally into mechanisms of peripheral immunoregulation and the development of novel immunosuppressives. 相似文献
992.
Synergistic interactions between cytokines underlie developmental processes fundamental to tissue and cellular engineering. However, a mechanistic understanding of the cell-specific and population-mediated effects is often lacking. In this study, we have investigated the synergistic generation of erythroid cells in response to erythropoietin (EPO) and stem cell factor (SCF). We have used a quantitative approach to determine if the effects of EPO and SCF superpose in a supra-additive fashion on the cell proliferation rate or on the death rate, suggesting a contribution from a joint cytokine effect (co-signaling). Primary mouse bone marrow hematopoietic cells and the stem cell-like FDCP-mix cell line were used to investigate the effects of EPO and SCF (individually or in combination) on erythroid output. Carboxyfluorescein diacetate succinimidyl ester (CFSE)-based cell-division tracking and mathematical modeling were used to measure cell type-specific proliferation and death rates. We observed a significant synergistic effect of EPO and SCF on the net generation of benzidine positive (erythroid) colony-forming cells, CD71++ (early erythroblasts) cells and TER-119+ (late erythroblasts and reticulocytes) cells in culture. When the observed increases in cell number were decomposed into proliferation and death rates, the cytokines were shown to act independently at different stages of erythroid development; SCF promoted the early proliferation of primitive cells, while EPO primarily promoted the survival of differentiating erythroid progenitor cells. Our analysis demonstrates that EPO and SCF have distinct and predominantly sequential effects on erythroid differentiation. This study emphasizes the necessity to separate proliferation rates from death rates to understand apparent cytokine synergies. 相似文献
993.
Furne J Saeed A Levitt MD 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(5):R1479-R1485
Hydrogen sulfide is gaining acceptance as an endogenously produced modulator of tissue function. The present paradigm of H(2)S (diprotonated, gaseous form of hydrogen sulfide) as a tissue messenger consists of H(2)S being released from the desulfhydration of l-cysteine at a rate sufficient to maintain whole tissue hydrogen sulfide concentrations of 30 microM to >100 microM, and these tissue concentrations serve a messenger function. Utilizing physiological concentrations of l-cysteine and aerobic conditions, we found that catabolism of hydrogen sulfide by mouse liver and brain homogenates exceeded the rate of enzymatic release of this compound such that measureable hydrogen sulfide release was less with tissue-containing vs. tissue-free buffers. Analyses of the gas space over rapidly homogenized mouse brain and liver indicated that in situ tissue hydrogen sulfide concentrations were only about 15 nM. Human alveolar air measurements indicated negligible free H(2)S concentrations in blood. We conclude rapid tissue catabolism of hydrogen sulfide maintains whole tissue brain and liver concentrations of free hydrogen sulfide that are three orders of magnitude less than conventionally accepted values and only 1/5,000 of the hydrogen sulfide concentration (100 microM) required to alter cellular function in vitro. For hydrogen sulfide to serve as an endogenously produced messenger, tissue production and catabolism must result in intracellular microenvironments with a sufficiently high hydrogen sulfide concentration to activate a local signaling mechanism, while whole tissue concentrations remain very low. 相似文献
994.
995.
Dragovich PS Blazel JK Ellis DA Han Q Kamran R Kissinger CR LeBrun LA Li LS Murphy DE Noble M Patel RA Ruebsam F Sergeeva MV Shah AM Showalter RE Tran CV Tsan M Webber SE Kirkovsky L Zhou Y 《Bioorganic & medicinal chemistry letters》2008,18(20):5635-5639
The synthesis of 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones bearing 6-amino substituents as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC(50)<0.10 microM). In vitro DMPK data (microsome t(1/2), Caco-2 P(app)) for many of the compounds are also disclosed, and a crystal structure of a representative inhibitor complexed with the NS5B protein is discussed. 相似文献
996.
Pasternak A Goble SD Vicario PP Di Salvo J Ayala JM Struthers M DeMartino JA Mills SG Yang L 《Bioorganic & medicinal chemistry letters》2008,18(3):994-998
This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the I(Kr) channel; poor selectivity against I(Kr) had been a liability of earlier analogs in this series. 相似文献
997.
Pasternak A Goble SD Doss GA Tsou NN Butora G Vicario PP Ayala JM Struthers M Demartino JA Mills SG Yang L 《Bioorganic & medicinal chemistry letters》2008,18(4):1374-1377
In an effort to shed light on the active binding conformation of our 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists, we prepared several conformationally constrained analogs resulting from backbone cyclization. Evaluation of CCR2 binding affinities for these analogs gave insight into the optimal relative positions of the piperidine and benzylamide moieties while simultaneously leading to the discovery of a new, potent lead type based upon a spirocyclic acetal scaffold. 相似文献
998.
Clarke B Demont E Dingwall C Dunsdon R Faller A Hawkins J Hussain I MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Soleil V Smith KJ Stanway S Stemp G Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1017-1021
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures. 相似文献
999.
Chisholm James S. Quinlivan Julie A. Petersen Rodney W. Coall David A. 《Human nature (Hawthorne, N.Y.)》2005,16(3):233-265
Life history theory suggests that in risky and uncertain environments the optimal reproductive strategy is to reproduce early
in order to maximize the probability of leaving any descendants at all. The fact that early menarche facilitates early reproduction
provides an adaptationist rationale for our first two hypotheses: that women who experience more risky and uncertain environments
early in life would have (1) earlier menarche and (2) earlier first births than women who experience less stress at an early
age. Attachment theory and research provide the rationale for our second two hypotheses: that the subjective early experience
of risky and uncertain environments (insecurity) is (3) part of an evolved mechanism for entraining alternative reproductive
strategies contingent on environmental risk and uncertainty and (4) reflected in expected lifespan. Evidence from our pilot
study of 100 women attending antenatal clinics at a large metropolitan hospital is consistent with all four hypotheses: Women
reporting more troubled family relations early in life had earlier menarche, earlier first birth, were more likely to identify
with insecure adult attachment styles, and expected shorter lifespans. Multivariate analyses show that early stress directly
affected age at menarche and first birth, affected adult attachment in interaction with expected lifespan, but had no effect
on expected lifespan, where its original effect was taken over by interactions between age at menarche and adult attachment
as well as age at first birth and adult attachment. We discuss our results in terms of the need to combine evolutionary and
developmental perspectives and the relation between early stress in general and father absence in particular.
This work was supported by The University of Melbourne Department of Obstetrics and Gynaecology.
James S. Chisholm is Professor in the School of Anatomy and Human Biology at the University of Western Australia. He is an
anthropologist whose interests lie in the fields of human behavioral biology, evolutionary ecology, life history theory, and
parental investment theory, where he focuses on infant social-emotional development, the development of reproductive strategies,
and the integration of evolutionary, developmental, and cultural psychology and public health.
Julie A. Quinlivan is Associate Professor in Obstetrics and Gynaecology at the University of Melbourne and Head of the Maternity
Care Program at the Royal Women’s Hospital, Melbourne. Her interests are teenage pregnancy, domestic violence, child abuse
prevention, and high-risk pregnancy.
Rodney W. Petersen is Senior Lecturer in Obstetrics and Gynaecology at the University of Melbourne and Senior Consultant in
Obstetrics and Gynaecology at the Royal Women’s Hospital and Sunshine Hospital in Melbourne. His interests are in psychosocial
aspects of women’s health and cancer.
David A. Coall is a Ph.D. student in the School of Anatomy and Human Biology at the University of Western Australia. His main
interest lies in the application of evolutionary theory within an epidemiological framework. He is currently working on the
synthesis of life history theory, parental investment theory, and parent-offspring conflict theory in exploring factors that
influence variation in human birth weight and placental weight. 相似文献
1000.