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981.
Loizon S Boeuf P Tetteh JK Goka B Obeng-Adjei G Kurtzhals JA Rogier C Akanmori BD Mercereau-Puijalon O Hviid L Behr C 《Microbes and infection / Institut Pasteur》2007,9(11):1252-1259
T cells are thought to play a critical role in cerebral malaria pathogenesis. However, available evidences are restricted to rodent models in which V beta specific T cell expansion has been associated with neurological syndrome suggesting involvement of superantigens or dominant antigens. Using flow cytometry, we studied the peripheral V beta T cell repertoire of Ghanaian children with cerebral malaria, uncomplicated malaria and asymptomatic control children, to look for either expansion or deletion of specific V beta associated with cerebral malaria. At admission, the general pattern of the repertoire of the patients was very similar, with no major distortion compared to the control group a part a significant increase of the frequency of the V beta 21.3 subset correlating with disease severity and attributed to the CD4 subset. During convalescence very limited fluctuations were observed including a significant decrease of the V beta 21.3 subset and increase of the V beta 20 subset, a subset not detected at admission. The remarkable stability of the V beta repertoire observed in acute malaria either cerebral or uncomplicated argues against the idea that cerebral malaria would result from a T cell-mediated inflammatory shock syndrome driven by some dominant super-antigenic activity(ies). The significance of the reproducible increase of the CD4+V beta 21.3T cell subset deserves further investigations. 相似文献
982.
Werner JM Eger K Jürgen Steinfelder H 《Apoptosis : an international journal on programmed cell death》2007,12(1):235-246
Trans-beta-nitrostyrene (TBNS) has been reported to be a potent inhibitor of protein phosphatases PTB1 and PP2A and to display a pro-apoptotic effect even in multidrug resistant tumour cells. Here we compared the anti-tumour potential of TBNS with 5-fluorouracil (5-FU) as the standard chemotherapeutic agent for colorectal cancer in LoVo cells. Resistance to 5-FU based therapy might be a consequence of 5-FU's delayed effect requiring long-term effective concentrations in the tumour tissue. Thus, alternatives like platin containing drugs with a more rapid effect have been introduced recently. Compared to 5-FU TBNS displayed a faster cytotoxic and pro-apoptotic effect. A 50% decrease in viability was observed already after 8 h with TBNS while 5-FU displayed no significant effect before 48 h. DNA fragmentation and caspase-3 assays confirmed the more rapid apoptotic effect of TBNS. Since apoptosis affects individual cells these results about a rapidly induced apoptosis were further studied on a single cell level in microscopic assays of caspase-3 and caspase-8 activation. Adducts of trans-beta-nitrostyrene displayed an anti-tumour effect comparable to TBNS which suggests the possibility of creating adducts with optimised tissue targeting. Finally, the calculation of a drug combination index displayed a synergistic effect for the combination of TBNS and 5-FU in Lovo as well as in HT-29 and HCT116 colon cancer cells. 相似文献
983.
Tritschler F Murín R Birk B Berger J Rapp M Hamprecht B Verleysdonk S 《Neurochemical research》2007,32(6):1028-1035
Ependymal cell culture models from rat have been developed over the last 20 years to facilitate biochemical studies on this
least-studied glial cell type. The cell culture protocol calls for the presence of thrombin, which is essential for obtaining
a high proportion of multiciliated ependymal cells. The serine protease appears to act via protease-activated receptor 1 to
prevent the apoptosis of ependymal precursors and enhance their proliferation without affecting contaminating cells. Unciliated
precursors differentiate into polyciliated ependymocytes by passing through a stage of monociliation. The message for protease-activated
receptor (PAR) 1 is initially abundant in the cultures, but its level declines as the cells differentiate. Besides PAR 1,
signalling through PAR 2 also promotes ciliation in rat brain primary cultures, albeit to a lesser degree than the thrombin
receptor. Thrombin and other proteases may be involved in the regulation of ventricular wall development. This action would
be mediated mainly by PAR1. 相似文献
984.
A novel method to monitor insulin-stimulated GTP-loading of Rab11a in cardiomyocytes 总被引:1,自引:0,他引:1
As a member of the Rab small GTPase family, Rab11a has been shown to be involved in different vesicle trafficking processes. In earlier work we identified Rab11a to be present in GLUT4-containing vesicles after insulin stimulation and showed its involvement in insulin-dependent glucose uptake. However, it remained elusive if Rab11a is directly activated by the insulin signalling cascade and at which step a potential activation occurs. To examine the GTP-loading of Rab11a, we introduced a biotinylated GTP-analog into H9c2-hIR cells, transiently overexpressing HA-tagged Rab11a, and measured its binding to the GTPase after insulin stimulation. We observed that Rab11a is transiently GTP-loaded after insulin stimulation with a 2.3 (+/-0.3) fold activation (n=5), reaching its maximum after 4 min and declining back to basal after additional 2 min. The activation of Rab11a is phosphatidylinositol 3-kinase (PI3-kinase) dependent and downstream of Akt, as shown by in vitro knockdown of this kinase. These data show that Rab11a is directly activated by insulin and represents an element of the GLUT4 trafficking machinery. 相似文献
985.
986.
Tribolium castaneum has telotrophic meroistic ovarioles of the Polyphaga type. During larval stages, germ cells multiply in a first mitotic cycle
forming many small, irregularly branched germ-cell clusters which colonize between the anterior and posterior somatic tissues
in each ovariole. Because germ-cell multiplication is accompanied by cluster splitting, we assume a very low number of germ
cells per ovariole at the beginning of ovariole development. In the late larval and early pupal stages, we found programmed
cell death of germ-cell clusters that are located in anterior and middle regions of the ovarioles. Only those clusters survive
that rest on posterior somatic tissue. The germ cells that are in direct contact with posterior somatic cells transform into
morphologically distinct pro-oocytes. Intercellular bridges interconnecting pro-oocytes are located posteriorly and are filled
with fusomes that regularly fuse to form polyfusomes. Intercellular bridges connecting pro-oocytes to pro-nurse cells are
always positioned anteriorly and contain small fusomal plugs. During pupal stages, a second wave of metasynchronous mitoses
is initiated by the pro-oocytes, leading to linear subclusters with few bifurcations. We assume that the pro-oocytes together
with posterior somatic cells build the center of determination and differentiation of germ cells throughout the larval, pupal,
and adult stages. The early developmental pattern of germ-cell multiplication is highly similar to the events known from the
telotrophic ovary of the Sialis type. We conclude that among the common ancestors of Neuropterida and Coleoptera, a telotrophic meroistic ovary of the Sialis type evolved, which still exists in Sialidae, Raphidioptera, and a myxophagan Coleoptera family, the Hydroscaphidae. Consequently,
the telotrophic ovary of the Polyphaga type evolved from the Sialis type.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
987.
Ripperger JA 《Genome biology》2007,8(8):313
A report on the symposium 'Clocks and Rhythms', Cold Spring Harbor, USA, 30 May-4 June 2007. 相似文献
988.
Han C Smolen JS Kavanaugh A van der Heijde D Braun J Westhovens R Zhao N Rahman MU Baker D Bala M 《Arthritis research & therapy》2007,9(5):R103
In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis
(RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the
HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies
of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and
24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL
at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the
diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS
cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores
compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab
and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with
RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those
in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled
studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly
greater improvement in HRQoL after treatment with infliximab. 相似文献
989.
Zuzarte M Rinné S Schlichthörl G Schubert A Daut J Preisig-Müller R 《Traffic (Copenhagen, Denmark)》2007,8(8):1093-1100
We have characterized a sequence motif, EDE, in the proximal C-terminus of the acid-sensitive potassium channel TASK-3. Human TASK-3 channels were expressed in Xenopus oocytes, and the density of the channels at the surface membrane was studied with two complementary techniques: a luminometric surface expression assay of hemagglutinin epitope-tagged TASK-3 channels and voltage-clamp measurements of the acid-sensitive potassium current. Both approaches showed that mutation of the two glutamate residues of the EDE motif to alanine (ADA mutant) markedly reduced the transport of TASK-3 channels to the cell surface. Mutation of the central aspartate of the EDE motif had no effect on surface expression. The functional role of the EDE motif was further characterized in chimaeric constructs consisting of truncated Kir2.1 channels to which the C-terminus of TASK-3 was attached. In these constructs, too, replacement of the EDE motif by ADA strongly reduced surface expression. Live-cell imaging of enhanced green fluorescent protein-tagged channels expressed in COS-7 cells showed that 24 h after transfection wild-type TASK-3 was mainly localized to the cell surface whereas the ADA mutant was largely retained in the endoplasmic reticulum (ER). Mutation of a second di-acidic motif in the C-terminus of TASK-3 (DAE) had no effect on surface expression. Coexpression of TASK-3 with a GTP-restricted mutant of the coat recruitment GTPase Sar1 (Sar1H79G) resulted in ER retention of the channel. Our data suggest that the di-acidic motif, EDE, in human TASK-3 is a major determinant of the rate of ER export and is required for efficient surface expression of the channel. 相似文献
990.
Environmental Biology of Fishes - Ex situ conservation comprises some of the oldest and best-known conservation methods and it has been applied for different fish stocks. This study describes... 相似文献