全文获取类型
收费全文 | 44566篇 |
免费 | 3169篇 |
国内免费 | 6327篇 |
出版年
2024年 | 35篇 |
2023年 | 651篇 |
2022年 | 764篇 |
2021年 | 1192篇 |
2020年 | 1192篇 |
2019年 | 1580篇 |
2018年 | 1254篇 |
2017年 | 1269篇 |
2016年 | 1332篇 |
2015年 | 1625篇 |
2014年 | 2213篇 |
2013年 | 2885篇 |
2012年 | 2049篇 |
2011年 | 2223篇 |
2010年 | 1846篇 |
2009年 | 2480篇 |
2008年 | 2666篇 |
2007年 | 2861篇 |
2006年 | 2762篇 |
2005年 | 2615篇 |
2004年 | 2344篇 |
2003年 | 2226篇 |
2002年 | 1933篇 |
2001年 | 1561篇 |
2000年 | 1305篇 |
1999年 | 1205篇 |
1998年 | 1056篇 |
1997年 | 854篇 |
1996年 | 810篇 |
1995年 | 872篇 |
1994年 | 802篇 |
1993年 | 600篇 |
1992年 | 521篇 |
1991年 | 443篇 |
1990年 | 364篇 |
1989年 | 265篇 |
1988年 | 285篇 |
1987年 | 236篇 |
1986年 | 172篇 |
1985年 | 165篇 |
1984年 | 140篇 |
1983年 | 81篇 |
1982年 | 98篇 |
1981年 | 63篇 |
1980年 | 53篇 |
1979年 | 34篇 |
1978年 | 27篇 |
1977年 | 14篇 |
1976年 | 20篇 |
1950年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response
to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in
different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders.
We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with
carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory
illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug
responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug
efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced
endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced
adaptations dissipate (the “time-off seizure” effect), leading to the re-emergence of seizures, a re-induction of a new, but
diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats,
an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance.
We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous
adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression
and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can
be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive
(decreasing the stimulation current.), increasing drug dosage, switching to a new drug that does not show crosstolerance to
the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal.
Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression
of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined
that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity
can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted
by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the
neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the
biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent
illness emergence and progression and its associated accumulating neurobiological, vulnerability factors. 相似文献
3.
Learning-Induced Expression of Meningeal Ependymin mRNA and Demonstration of Ependymin in Neurons and Glial Cells 总被引:1,自引:0,他引:1
Stefan Rother Rupert Schmidt Wolfgang Brysch †Karl-Hermann Schlingensiepen 《Journal of neurochemistry》1995,65(4):1456-1464
Abstract: The turnover of a CNS-specific cell adhesion glycoprotein, ependymin, has earlier been found to increase during periods of neuronal plasticity. Here, ependymin mRNA expression was analyzed by semiquantitative in situ hybridization in goldfish. Learning of an active avoidance response resulted in a significant increase in ependymin mRNA expression 20 min to 4 h after acquisition of the task. In contrast, yoked control animals that were exposed to the same numbers of conditioned and unconditioned stimuli in a random, unpaired manner exhibited a strong down-regulation of ependymin mRNA. Hybridization signals were also increased by injection of anti-ependymin antiserum into brain ventricles. Ependymin mRNA was exclusively localized to reticular-shaped fibroblasts of the inner endomeningeal cell layer. Immunoelectron microscopic investigation, however, revealed ependymin also in distinct neuronal and glial cell populations in which no ependymin mRNA had been detected. Uptake of meningeal protein factors into glial and neuronal cells may therefore be of functional importance for plastic adaptations of the CNS. 相似文献
4.
Protein secretion in streptomycetes 总被引:1,自引:0,他引:1
5.
6.
7.
Streptococcus pyogenes is commonly found on pharynx, mouth and rarely on skin, lower gastrointestinal tract. It is a potential pathogen causing tonsillitis, pneumonia, endocarditis. The present study was undertaken to study the effects of low shear modeled microgravity on growth, morphology, antibiotic resistance, cross-stress resistance to various stresses and alteration in gene expression of S. pyogenes. The growth analysis performed using UV–Visible spectroscopy indicated decrease in growth of S. pyogenes under low shear modeled microgravity. Morphological analysis by Bio-transmission electron microscopy (TEM), Bio-scanning electron microscopy (SEM) did not reveal much difference between normal and low shear modeled microgravity grown S. pyogenes. The sensitivity of S. pyogenes to antibiotics ampicillin, penicillin, streptomycin, kanamycin, hygromycin, rifampicin indicates that the bacterium is resistant to hygromycin. Further S. pyogenes cultured under low shear modeled microgravity was found to be more sensitive to ampicillin and rifampicin as compared with normal gravity grown S. pyogenes. The bacteria were tested for the acid, osmotic, temperature and oxidative cross stress resistances. The gene expression of S. pyogenes under low shear modeled microgravity analyzed by microarray revealed upregulation of 26 genes and down regulation of 22 genes by a fold change of 1.5. 相似文献
8.
Conservation genetics considerations in fishery management 总被引:1,自引:0,他引:1
N. Ryman 《Journal of fish biology》1991,39(SA):211-224
9.
Mark A. Schembri Alan A. Woods Ronald C. Bayly John K. Davies 《FEMS microbiology letters》1995,133(3):277-283
Abstract Transferrin-binding proteins from Neisseria meningitidis vary among different isolates. We have identified and studied a hypervariable region adjacent to the carboxyl-end of the transferrin-binding domain of the Tbp2 molecule. The tbp2 genes from six strains of N. meningitidis were cloned and sequenced in this particular region. Sequence analysis of these regions along with five other sequences available from pathogenic Neisseria showed a common organisation of seven highly variable nucleotide stretches interspersed with six conserved nucleotide stretches. The variable regions correlated with the location of immunoreactive epitopes in polyclonal antisera raised to transferrin-binding proteins identified by peptide pin technology. Sequence analysis suggested a mosaic-like organisation of the tbp2 genes. Taken together, these data suggest that the antigenic variation in this part of the protein may result from a strong host immune pressure. 相似文献
10.
Jiefeng He Haichao Zhao Dongfeng Deng Yadong Wang Xiao Zhang Haoliang Zhao Zongquan Xu 《Journal of cellular physiology》2020,235(3):2464-2477
This study aimed to identify significant biomarkers related to the prognosis of liver cancer using long noncoding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) analysis. Differentially expressed mRNA and lncRNAs between liver cancer and paracancerous tissues were screened, and the functions of these mRNAs were predicted by gene ontology and pathway enrichment analyses. A ceRNA network consisting of differentially expressed mRNAs and lncRNAs was constructed. LncRNA FENDRR and lncRNA HAND2-AS1 were hub nodes in the ceRNA network. A risk score assessment model consisting of eight genes (PDE2A, ESR1, FBLN5, ALDH8A1, AKR1D1, EHHADH, ADRA1A, and GNE) associated with prognosis were developed. Multivariate Cox regression suggested that both pathologic_T and risk group could be regarded as independent prognostic factors. Furthermore, a nomogram model consisting of pathologic_T and risk group showed a good prediction ability for predicting the survival rate of liver cancer patients. The nomogram model consisting of pathologic_T and a risk score assessment model could be regarded as an independent factor for predicting prognosis of liver cancer. 相似文献