全文获取类型
收费全文 | 150737篇 |
免费 | 5521篇 |
国内免费 | 854篇 |
出版年
2021年 | 1008篇 |
2020年 | 831篇 |
2019年 | 920篇 |
2018年 | 12751篇 |
2017年 | 11439篇 |
2016年 | 9024篇 |
2015年 | 3158篇 |
2014年 | 2879篇 |
2013年 | 3512篇 |
2012年 | 7912篇 |
2011年 | 15987篇 |
2010年 | 13889篇 |
2009年 | 10088篇 |
2008年 | 12126篇 |
2007年 | 13644篇 |
2006年 | 2601篇 |
2005年 | 3114篇 |
2004年 | 3556篇 |
2003年 | 3184篇 |
2002年 | 2548篇 |
2001年 | 1783篇 |
2000年 | 1612篇 |
1999年 | 1337篇 |
1998年 | 620篇 |
1997年 | 600篇 |
1996年 | 625篇 |
1995年 | 523篇 |
1994年 | 536篇 |
1993年 | 526篇 |
1992年 | 1039篇 |
1991年 | 938篇 |
1990年 | 847篇 |
1989年 | 828篇 |
1988年 | 816篇 |
1987年 | 749篇 |
1986年 | 708篇 |
1985年 | 692篇 |
1984年 | 651篇 |
1983年 | 493篇 |
1982年 | 384篇 |
1981年 | 381篇 |
1980年 | 345篇 |
1979年 | 491篇 |
1978年 | 404篇 |
1977年 | 325篇 |
1975年 | 331篇 |
1974年 | 330篇 |
1973年 | 330篇 |
1972年 | 481篇 |
1971年 | 486篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
41.
Late Quaternary climate change,relict populations and present‐day refugia in the northern Atacama Desert: a case study from Quebrada La Higuera (18° S) 下载免费PDF全文
42.
43.
Gro O. Nygaard Elisabeth G. Celius Sigrid A. de Rodez Benavent Piotr Sowa Marte W. Gustavsen Anders M. Fjell Nils I. Landr? Kristine B. Walhovd Hanne F. Harbo 《PloS one》2015,10(8)
New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity. 相似文献
44.
Graziele Fonseca de Sousa Maira de Assis Lima Débora Fernandes Custodio Vanessa Morais Freitas Gisele Monteiro 《PloS one》2015,10(12)
The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NEDDylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance. 相似文献
45.
Min Soo Byun Song E. Kim Jinsick Park Dahyun Yi Young Min Choe Bo Kyung Sohn Hyo Jung Choi Hyewon Baek Ji Young Han Jong Inn Woo Dong Young Lee Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2015,10(11)
We aimed to identify and characterize subtypes of Alzheimer’s disease (AD) exhibiting different patterns of regional brain atrophy on MRI using age- and gender-specific norms of regional brain volumes. AD subjects included in the Alzheimer''s Disease Neuroimaging Initiative study were classified into subtypes based on standardized values (Z-scores) of hippocampal and regional cortical volumes on MRI with reference to age- and gender-specific norms obtained from 222 cognitively normal (CN) subjects. Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes. Whole-brain-level gray matter (GM) atrophy pattern using voxel-based morphometry (VBM) and cerebrospinal fluid (CSF) biomarkers of the subtypes were also investigated. Of 163 AD subjects, 58.9% were classified as the “both impaired” subtype with the typical hippocampal and cortical atrophy pattern, whereas 41.1% were classified as the subtypes with atypical atrophy patterns: “hippocampal atrophy only” (19.0%), “cortical atrophy only” (11.7%), and “both spared” (10.4%). Voxel-based morphometric analysis demonstrated whole-brain-level differences in overall GM atrophy across the subtypes. These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-β1–42 levels compared to CN. In conclusion, we identified four AD subtypes exhibiting heterogeneous atrophy patterns on MRI with different progression rates after controlling the effects of aging and gender on atrophy with normative information. CSF biomarker analysis suggests the presence of Aβ neuropathology irrespective of subtypes. Such heterogeneity of MRI-based neuronal injury biomarker and related heterogeneous progression patterns should be considered in clinical trials and practice with AD patients. 相似文献
46.
Senescent, naturally dried leaves of Typha domingensis were incubated inthe littoral region of a coastal lagoon and epiphytic bacterial volume,abundance, biomass and secondary productivity were measured during 127 daysof decomposition. The peak of cell abundance was registered at t =127 days when expressed per leaf surface area (10.07×107cells cm-2; 7.26 µgC cm-2), and at t= 26 days when expressed per biofilm dry mass (38.10 ×107 cells (mgDM biofilm)-1, 30.52 µgC(mgDM biofilm)-1). The highest values of bacterial biovolumesand lower turnover time were usually obtained in the beginning of thecolonization. Leu:Tdr ratios were also higher in the beginning of thecolonization, when bacterial community presented unbalanced metabolism.Consequently, the highest discrepancies between the bacterial secondaryproduction estimated by leu and Tdr incorporation were observed in the first2 days of decomposition. On average, the bacterial secondary productivityestimated by leu incorporation was 2.1 times higher than the valuesestimated by Tdr incorporation when the empirical factor for Tdr wasobtained from the relationship between Tdr and biomass increment. Thisdifference increased to 4.2 when the empirical factor was obtained from therelationship between Tdr and cell numbers increment. An average of bothmethods (0.0037 to 0.1397 µgC cm-2 h-1)produced results that fall within the range reported in the literature forepiphytic bacteria of freshwater ecosystems. 相似文献
47.
M. P. Fuggetta E. Alvino R. Pepponi R. de Filippi S. Marini E. Bonmassar 《Cell proliferation》1993,26(4):305-316
There is general agreement that several distinct subpopulations of lymphocytes, including major histocompatibility complex (MHC)-restricted T lymphocytes and non-restricted natural killer, or lymphokine-activated killer (LAK), cells are active in lysing neoplastic cells. In this study experiments were designed to compare the inhibitory effects of LAK cells and allosensitized cytotoxic T lymphocytes (CTL) on in vitro growth of an Epstein–Barr virus-transformed B-cell line (BSM) and of a HTLV-I producer T-cell line (MT-2). It was found that allosensitized CTL are more efficient at inducing BSM, or MT-2, cell growth inhibition than LAK cells. These results are consistent with the hypothesis that MHC-restricted T effector cells could mediate higher tumour suppressive effects than non-MHC restricted LAK cells. 相似文献
48.
Selma Soares de Oliveira Sandra Amaral de Araújo Maria do Carmo de Freire Bastos 《FEMS microbiology letters》1993,106(2):123-127
Abstract A 5.8-kb Cla I fragment of pRJ9, a bacteriocinogenic plasmid of Sphylococcus aureus , was cloned in the unique Cla I site of pRJ5. The recombinant plasmid obtained, pRJ23, failed to confer bacteriocin production and immunity to bacteriocin on host cells. The cloned fragment was shown to contain the complete replicon of pRJ9. Attempts to clone the 4.4-kb Cla I fragment of pRJ9 were unsuccessful, apparently due to the inactivation of the basic replicon of the cloning vector. Therefore, plasmid pRJ5 cut at its Cla I site appears to be a suitable vector for cloning replication regions of plasmids that cab replicate in S. aureus . 相似文献
49.
S Kotake M D de Smet B Wiggert T M Redmond G J Chader I Gery 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(9):2995-3001
Interphotoreceptor retinoid-binding protein (IRBP), a retinal-specific Ag, induces experimental autoimmune uveitis in a variety of animals. We have previously shown that sequence 1169-1191 of bovine IRBP is the immunodominant epitope of this protein in Lewis rats and is highly immunogenic and uveitogenic in these rats. The active site of peptide 1169-1191 was determined by testing its truncated forms. The shortest peptide to be immunologically active was found to be 1182-1190 (WEGVGVVPD). To determine the role of individual residues of this sequence, we have tested the immunologic activities of nine analogs of peptide 1181-1191, in which each of residues 1182-1190 was substituted with alanine (A). The tested activities included the capacity to induce experimental autoimmune uveitis and cellular responses in immunized rats, as well as the capability to stimulate lymphocytes sensitized against IRBP or the parent peptide 1181-1191. Analogs that did not stimulate these lymphocytes were also tested for their capacity to competitively inhibit the proliferative response to 1181-1191. Analogs A(1184), A(1186), and A(1187) resembled 1181-1191 in their activities, whereas the other analogs exhibited remarkably reduced activities, with several patterns being noticed. Analog A(1182) was inactive in all tests. Analog A(1190) was very weakly uveitogenic and non-immunogenic, but it stimulated lymphocytes sensitized against IRBP or 1181-1191 when added at exceedingly high concentrations. Analogs A(1183) and A(1185) resembled A(1190) in being weakly uveitogenic and A(1185) was also found to be poorly immunogenic. In addition, relatively high concentrations of A(1183) and A(1185) were needed to stimulate lymphocytes sensitized against IRBP or 1181-1191. However, a different pattern of activities was exhibited by analogs A(1188) and A(1189). These peptides were uveitogenic and immunogenic, but failed to stimulate lymphocytes sensitized to IRBP or 1181-1191. Furthermore, A(1188) and A(1189), but not A(1182), also inhibited the response to 1181-1191 of a cell line specific toward this parent peptide. The data are interpreted to show that residues 1188 and 1189 are involved in the interaction of the peptide with the TCR, whereas residues 1182 and 1190 and, perhaps, 1183 and 1185, are pivotal for the binding of peptide 1181-1190 to the MHC molecules on APC. 相似文献
50.
Crystals of the complex between human growth hormone and the extracellular domain of its receptor. 总被引:2,自引:0,他引:2
Single crystals suitable for high-resolution diffraction studies have been grown of the human growth hormone (hGH) complexed to the extracellular domain of its cloned receptor from the human liver (hGHbp), using the technique of repeat seeding. The crystals are in space group P2(1)2(1)2, with a = 145.8 A, b = 68.6 A, c = 76.0 A, and diffract to at least 2.7 A resolution on a rotating anode X-ray source. Analysis of the composition of these crystals showed the stoichiometry of the complex to be hGH: (hGHbp)2. This finding, coupled with biochemical data on the complex in solution, indicates that the biologically significant dimerization of the growth hormone receptor is mediated through a single hormone molecule. Structure determination of the complex is currently being completed. 相似文献