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951.
Human glioma cell culture: two FCS-free media could be recommended for clinical use in immunotherapy
Anne Clavreul Isabelle Jean Laurence Preisser Agnès Chassevent Anne Sapin Sophie Michalak Philippe Menei 《In vitro cellular & developmental biology. Animal》2009,45(9):500-511
Immunotherapy, particularly active vaccination, may be developed as an effective and safe treatment modality for malignant
gliomas, which continue to have a poor prognosis, despite advances in surgical techniques and adjuvant chemotherapy and radiotherapy.
Since no glioma-specific tumor-associated antigens (TAAs) have been discovered, autologous tumor cells or well-established
glioma cell lines could be used in future vaccination protocols to induce antitumour immunity against unknown TAAs. One obstacle
for clinical use of these tumour cell vaccines is related to foetal calf serum (FCS). Efforts are currently being directed
toward developing FCS-free media and serum-free alternatives to culture these cell vaccines. In this study, a medium containing
human serum and one serum-free medium (UltraCulture), supplemented or not with epidermal growth factor, were tested on morphology,
survival, DNA content and TAA expression of human glioma cell lines and glioma biopsy primary cultures. Their effects were
compared on FCS-containing medium. Results show that, whatever the medium used, no significant variations in morphology and
survival were observed. Furthermore, human serum-containing medium or UltraCulture preserved at early passage cultures the
cell population of interest present in the biopsies before culture. In addition, the expression profile of eight TAAs was
similar between these media. These data indicate that human serum-containing medium and UltraCulture serum-free medium could
be promising candidates to produce tumour-cell vaccines. 相似文献
952.
Hans-Peter Rusterholz Marion Kissling Bruno Baur 《Perspectives in Plant Ecology, Evolution and Systematics》2009,11(1):17-29
Disturbances play a major role in structuring the community composition in a variety of ecosystems. The potential impact of disturbances on sexual reproduction and genetic diversity of plants has so far received little attention. We examined the effects of disturbance by human trampling on the performance, sexual reproduction and clonal diversity in the woodland herb Anemone nemorosa in six sites disturbed by intensive recreational activities and in six undisturbed sites in suburban forests in Switzerland. Disturbance by human trampling decreased shoot height of A. nemorosa and altered the size-dependent flowering probability function. Furthermore, in disturbed sites an increased percentage of aborted seeds was found, resulting in a reduced sexual reproductive potential of A. nemorosa populations. Both clonal and genetic diversity of A. nemorosa were reduced in disturbed sites. Our study shows for the first time that disturbance by human trampling can decrease the genetic diversity in a clonal woodland plant. This suggests that genetic aspects of woodland plants should be considered in restoring degenerated forest sites. 相似文献
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954.
Martin S Cosset EC Terrand J Maglott A Takeda K Dontenwill M 《Biochimica et biophysica acta》2009,1793(2):354-367
Caveolin-1 plays a checkpoint function in the regulation of processes often altered in cancer. Although increased expression of caveolin-1 seems to be the norm in the glioma family of malignancies, populations of caveolin-1 positive and negative cells coexist among glioblastoma specimens. As no data are available to date on the contribution of such cells to the phenotype of glioblastoma, we manipulated caveolin-1 in the glioblastoma cell line U87MG. We showed that caveolin-1 plays a critical role in the aggressiveness of glioblastoma. We identified integrins as the main set of genes affected by caveolin-1. We reported here that the phenotypic changes observed after caveolin-1 modulation were mediated by alpha(5)beta(1) integrins. As a consequence of the regulation of alpha(5)beta(1) levels by caveolin-1, the sensitivity of cells to the specific alpha(5)beta(1) integrin antagonist, SJ749, was affected. Mediator of caveolin-1 effects, alpha(5)beta(1) integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype. 相似文献
955.
Sophie Badie Chunyan Liao Maria Thanasoula Paul Barber Mark A. Hill Madalena Tarsounas 《The Journal of cell biology》2009,185(4):587-600
The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51 during DNA repair also exists, but its function in this context is not understood. In this study, we demonstrate that RAD51C accumulates at DNA damage sites concomitantly with the RAD51 recombinase and is retained after RAD51 disassembly, which is consistent with both an early and a late function for RAD51C. RAD51C recruitment depends on ataxia telangiectasia mutated, NBS1, and replication protein A, indicating it functions after DNA end resection but before RAD51 assembly. Furthermore, we find that RAD51C is required for activation of the checkpoint kinase CHK2 and cell cycle arrest in response to DNA damage. This suggests that hRAD51C contributes to the protection of genome integrity by transducing DNA damage signals in addition to engaging the HR machinery. 相似文献
956.
Sophie Marion de Procé Daniel L. Halligan Peter D. Keightley Brian Charlesworth 《Journal of molecular evolution》2009,69(6):601-611
Contrary to the classical view, a large amount of non-coding DNA seems to be selectively constrained in Drosophila and other
species. Here, using Drosophila miranda BAC sequences and the Drosophila pseudoobscura genome sequence, we aligned coding and non-coding sequences between D. pseudoobscura and D. miranda, and investigated their patterns of evolution. We found two patterns that have previously been observed in comparisons between
Drosophila melanogaster and its relatives. First, there is a negative correlation between intron divergence and intron length, suggesting that longer
non-coding sequences may contain more regulatory elements than shorter sequences. Our other main finding is a negative correlation
between the rate of non-synonymous substitutions (d
N) and codon usage bias (F
op), showing that fast-evolving genes have a lower codon usage bias, consistent with strong positive selection interfering with
weak selection for codon usage. 相似文献
957.
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959.
Nicolas Taulet Franck Comunale Cyril Favard Sophie Charrasse St��phane Bodin C��cile Gauthier-Rouvi��re 《The Journal of biological chemistry》2009,284(34):23137-23145
p120 catenin is a major regulator of cadherin stability at cell-cell contacts and a modulator of Rho GTPase activities. In C2C12 myoblasts, N-cadherin is stabilized at cell contacts through its association with cholesterol-rich membrane domains or lipid rafts (LR) and acts as an adhesion-activated receptor that activates RhoA, an event required for myogenesis induction. Here, we report that association of p120 catenin with N-cadherin at cell contacts occurs specifically in LR. We demonstrate that interaction of p120 catenin with N-cadherin is required for N-cadherin association with LR and for its stabilization at cell contacts. LR disruption inhibits myogenesis induction and N-cadherin-dependent RhoA activation as does the perturbation of the N-cadherin-p120 catenin complex after p120 catenin knockdown. Finally, we observe an N-cadherin-dependent accumulation of RhoA at phosphatidylinositol 4,5-bisphosphate-enriched cell contacts which is lost after LR disruption. Thus, a functional N-cadherin-catenin complex occurs in cholesterol-rich membrane microdomains which allows the recruitment of RhoA and the regulation of its activity during myogenesis induction.Skeletal myogenesis is a multistep process regulated by diffusible molecules and the interaction of muscle cell precursors with their neighbors and the extracellular matrix (1, 2). Particularly, N-cadherin-dependent intercellular adhesion has a major role in cell cycle exit and induction of skeletal muscle differentiation through activation of the Rho family GTPases. RhoA positively regulates MyoD expression and skeletal muscle differentiation because it is required for serum response factor-mediated activation of several muscle-specific gene promoters (3, 4).Dynamic association of cadherin complexes at the plasma membrane (PM)4 is crucial for cadherin-mediated signaling. Their extracellular domain mediates homophilic cell-cell adhesion, whereas the intracellular domain associates with catenins that produce attachment sites for the F-actin cytoskeleton (5–7). The juxtamembrane domain of the cadherin cytoplasmic tail binds to p120 catenin, which regulates cadherin stability at cell contacts and modulates Rho GTPase activities (8–11). Cadherin stability is directly dependent on p120 catenin, and in its absence most cadherins are internalized and often degraded, suggesting that p120 catenin controls cadherin turnover at the cell surface (11, 12). Moreover, mutations in the E-cadherin region that bind to p120 catenin dissociate the E-cadherin-p120 catenin complex and disrupt strong cell adhesion, although interaction with other catenins remains intact (13). Cadherin stability at cell-cell contacts is also regulated by homophilic binding between extracellular domains and association with the F-actin cytoskeleton (14, 15). Association of N-cadherin with cholesterol-enriched microdomains, called lipid rafts (LR), at cell contacts, also stabilizes N-cadherin (16). Because p120 catenin interaction with cadherins and N-cadherin association with LR at cell contact sites are both involved in cadherin stability at cell contact sites, we asked whether p120 catenin association with N-cadherin required LR. We observed that their association occurred specifically in these cholesterol-rich domains. Moreover, using an N-cadherin mutant unable to bind to p120 catenin, we showed that the N-cadherin/p120 catenin interaction was required for N-cadherin association with LR and its stabilization at cell contacts. Because N-cadherin is implicated in the commitment to myogenesis through RhoA activation, we questioned whether its association with p120 catenin in LR was a prerequisite for RhoA activation. LR disruption inhibited myogenesis induction, association of p120 catenin with N-cadherin, and N-cadherin-dependent RhoA activation, as did the perturbation of the N-cadherin-p120 catenin complex after p120 catenin knockdown. Together, these data suggest a crucial role for the N-cadherin/p120 catenin association in LR in the regulation of RhoA activity during myogenesis induction. 相似文献
960.