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311.
The mating system of the Mediterranean monk seal was studied combining the use of diverse technologies. Sexual dimorphism in size was limited. Sexual activity was only observed to occur in the water. The different segments of the population segregated spatially: females, pups, and juveniles aggregated inside two main caves, whose entrances were controlled by a small number (2–3) of territorial males that defended aquatic territories situated at the very mouth of the caves. Other territorial males defended aquatic territories located further away (5–30 km). The tenure of aquatic territories was nonseasonal and spanned several years. Relatedness among pups belonging to the same cohort was low or null, indicating a low level of polygyny, which is not surprising for an aquatically mating phocid with a protracted reproductive season. However, in addition, genetic relatedness showed a remarkable temporal periodicity. These results in combination point to the existence of a complex social structure in this species. 相似文献
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Laura Alías Sara Bernal Pablo Fuentes-Prior María Jesus Barceló Eva Also Rebeca Martínez-Hernández Francisco J. Rodríguez-Alvarez Yolanda Martín Elena Aller Elena Grau Ana Peciña Guillermo Antiñolo Enrique Galán Alberto L. Rosa Miguel Fernández-Burriel Salud Borrego José M. Millán Concepción Hernández-Chico Montserrat Baiget Eduardo F. Tizzano 《Human genetics》2009,125(1):29-39
Spinal muscular atrophy (SMA) is caused by mutations in the SMN1 gene. We have studied the molecular pathology of SMA in 745 unrelated Spanish patients using PCR-RFLP, SMN gene dosage analysis, linkage studies, long-range PCR and direct sequencing. Our systematic approach allowed us to complete
genetic testing and risk assessment in 736 SMA patients (98.8%). Females were more frequently affected by the acute form of
the disease (type I), whereas chronic forms (type II–III) predominated in males (p < 0.008). Absence of the SMN1 gene was detected in 671 patients (90%), and hybrid SMN1–SMN2 genes were observed in 37 cases (5%). Furthermore, we detected 13 small mutations in 28 patients (3.8%), four of which were
previously identified in other populations (c.91dupT; c.770_780dup11; p.Tyr272Cys and p.Thr274Ile), while five mutations were
found to date only in Spanish patients (c.399_402delAGAG, p.Ile116Phe, p.Gln136Glu, c.740dupC and c.834+2T>G). The c.399_402delAGAG
mutation accounted for 1.9% of all Spanish SMA patients. Finally, we discovered four novel mutations: c.312dupA, c.411delT,
p.Trp190X and p.Met263Thr. Our results confirm that most SMA cases are due to large genetic rearrangements in the repetitive
region of the SMA locus, resulting in absence-dysfunction of the SMN1 gene. By contrast, ancestrally inherited small mutations are responsible for only a small number of cases. Four prevalent
changes in exons 3 and 6 (c.399_402delAGAG; c.770_780dup11; p.Tyr272Cys; p.Thr274Ile) accounted for almost 70% of our patients
with these subtle mutations. An SMN–SMN dimer model featuring tight hydrophobic-aromatic interactions is proposed to explain
the impact of mutations at the C-terminal end of the protein. 相似文献
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Lo SM Follmer NE Lengsfeld BM Madamba EV Seong S Grau DJ Francis NJ 《Molecular cell》2012,46(6):784-796
Epigenetic regulation may involve heritable chromatin states, but how chromatin features can be inherited through DNA replication is incompletely understood. We address this question using cell-free replication of chromatin. Previously, we showed that a Polycomb group complex, PRC1, remains continuously associated with chromatin through DNA replication. Here we investigate the mechanism of persistence. We find that a single PRC1 subunit, Posterior sex combs (PSC), can reconstitute persistence through DNA replication. PSC binds nucleosomes and self-interacts, bridging nucleosomes into a stable, oligomeric structure. Within these structures, individual PSC-chromatin contacts are dynamic. Stable association of PSC with chromatin, including through DNA replication, depends on PSC-PSC interactions. Our data suggest that labile individual PSC-chromatin contacts allow passage of the DNA replication machinery while PSC-PSC interactions prevent PSC from dissociating, allowing it to rebind to replicated chromatin. This mechanism may allow inheritance of chromatin proteins including PRC1 through DNA replication to maintain chromatin states. 相似文献
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Injury-induced overexpression of tumor necrosis factor alpha (TNFα) in the spinal cord can induce chronic neuroinflammation and excitotoxicity that ultimately undermines functional recovery. Here we investigate how TNFα might also act to upset spinal function by modulating spinal plasticity. Using a model of instrumental learning in the injured spinal cord, we have previously shown that peripheral intermittent stimulation can produce a plastic change in spinal plasticity (metaplasticity), resulting in the prolonged inhibition of spinal learning. We hypothesized that spinal metaplasticity may be mediated by TNFα. We found that intermittent stimulation increased protein levels in the spinal cord. Using intrathecal pharmacological manipulations, we showed TNFα to be both necessary and sufficient for the long-term inhibition of a spinal instrumental learning task. These effects were found to be dependent on glial production of TNFα and involved downstream alterations in calcium-permeable AMPA receptors. These findings suggest a crucial role for glial TNFα in undermining spinal learning, and demonstrate the therapeutic potential of inhibiting TNFα activity to rescue and restore adaptive spinal plasticity to the injured spinal cord. TNFα modulation represents a novel therapeutic target for improving rehabilitation after spinal cord injury. 相似文献
319.
Pernas M Casado C Arcones C Llano A Sánchez-Merino V Mothe B Vicario JL Grau E Ruiz L Sánchez J Telenti A Yuste E Brander C Galíndez CL 《PloS one》2012,7(2):e31928
Objective
To study the causes for the lack of clinical progression in a superinfected HIV-1 LTNP elite controller patient.Methodology and Principal Findings
We studied host genetic, virological and immunological factors associated with viral control in a SI long term non progressor elite controller (LTNP-EC). The individual contained both viruses and maintained undetectable viral loads for >20 years and he did not express any of the described host genetic polymorphisms associated with viral control. None of four full-length gp160 recombinants derived from the LTNP-EC replicated in heterologous peripheral blood mononuclear cells. CTL responses after SI were maintained in two samples separated by 9 years and they were higher in breadth and magnitude than responses seen in most of 250 treatment naïve patients and also 25 controller subjects. The LTNP-EC showed a neutralization response, against 4 of the 6 viruses analyzed, superior to other ECs.Conclusions
The study demonstrated that a strong and sustained cellular and humoral immune response and low replicating viruses are associated with viral control in the superinfected LTNP-EC. 相似文献320.