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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.
T. A. Jaarsma E. Lohmanns H. Hendriks T. W. J. Gadella T. M. Malingré 《Plant Systematics and Evolution》1990,169(1-2):31-39
InS. tuberosum subspp.tuberosum andnodosum, S. grandiflorum andS. ibericum the presence of the pyrrolizidine alkaloids lycopsamine, echimidine and symphytine could be demonstrated. The taxonS. tuberosum contains an unknown compound that seems to be specific for this taxon. This compound is not the pyrrolizidine alkaloid anadoline which has previously been reported for this species. It is possibly represented by a peak on GC/MS with a molecular ion peak at m/z 623 (as TMS derivative) and can be used as a chemotaxonomic marker for the speciesS. tuberosum. The pyrrolizidine alkaloid pattern of the two subspecies ofS. tuberosum reinforces the close relationship. Fresh material ofS. tuberosum contained the triterpene isobauerenol, but in herbarium material isobauerenol was lacking. InS. grandiflorum, neither fresh nor dried material contains isobauerenol. In herbarium material ofS. ibericum also no isobauerenol could be found. More extensive chemotaxonomical research is necessary to support the view thatS. abchasicum is more closely related toS. ibericum than toS. grandiflorum. 相似文献
4.
Protein secretion in streptomycetes 总被引:1,自引:0,他引:1
5.
6.
《Harmful algae》2015
A differential screening study using high-resolution (HR)-hydrophilic interaction chromatography (HILIC)-electrospray ionization (ESI)–quadrupole time-of-flight mass spectrometry (Q-TOF MS) was conducted to identify saxitoxin (STX) analogues in the marine dinoflagellate toxic sub-clone Alexandrium tamarense Axat-2 and the non-toxic sub-clone UAT-014-009 derived from the same Japanese isolate. One unknown compound was identified only in the toxic sub-clone and was found to have the molecular formula C9H16N6O2. This structure differed from that of decarbamoyl STX (dcSTX; C9H16N6O3) by the loss of a single oxygen. A 12-deoxy-dcSTX standard (a mixture of 12α- and β-deoxy-dcSTX) was chemically prepared from dcSTX by reduction with sodium borohydride. The unknown compound in the toxic strain of A. tamarense was identified as 12β-deoxy-dcSTX by comparison of its HR-HILIC-LC–MS retention time and HR–MS/MS spectrum with those of the chemically prepared standard, and the identification was confirmed by high-sensitivity HPLC analysis with post-column fluorescent derivatization. Moreover, two Japanese isolates of A. catenella showing toxin profiles different from that of A. tamarense were also found to contain 12β-deoxy-dcSTX. Previously, 12β-deoxy-dcSTX was isolated from the freshwater cyanobacterium Lyngbya wollei, which produces a unique set of STX analogues. This study is the first evidence of the presence of 12β-deoxy-dcSTX in marine dinoflagellates. 相似文献
7.
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