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91.
Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity 下载免费PDF全文
Dey B Pancera M Svehla K Shu Y Xiang SH Vainshtein J Li Y Sodroski J Kwong PD Mascola JR Wyatt R 《Journal of virology》2007,81(11):5579-5593
The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations in several gp120 envelope glycoprotein contexts. The gp120 glycoproteins with the T257S-plus-S375W double mutation (T257S+S375W) have a superior antigenic profile compared to the originally identified single S375W replacement in terms of enhanced recognition by the broadly neutralizing CD4 binding-site antibody b12. Isothermal titration calorimetry measuring the entropy of the gp120 interaction with CD4 indicated that the double mutant was also stabilized into the CD4-bound state, with increasing relative fixation between core, full-length monomeric, and full-length trimeric versions of gp120. A significant increase in gp120 affinity for CD4 was also observed for the cavity-filling mutants relative to wild-type gp120. The most conformationally constrained T257S+S375W trimeric gp120 proteins were selected for immunogenicity analysis in rabbits and displayed a trend of improvement relative to their wild-type counterparts in terms of eliciting neutralizing antibodies. Together, the results suggest that conformational stabilization may improve the ability of gp120 to elicit neutralizing antibodies. 相似文献
92.
Gupta A Chattopadhyay I Dey S Nasipuri P Das SK Gangopadhyay PK Ray K 《Cellular and molecular neurobiology》2007,27(8):1023-1033
Aims We aim to identify the molecular defects in the ATP7B, the causal gene for Wilson disease (WD), in eastern Indian patients and attempt to assess the overall mutation spectrum
in India for detection of mutant allele for diagnostic purposes. Methods Patients from 109 unrelated families and their first-degree relatives comprising 400 individuals were enrolled in this study
as part of an ongoing project. Genomic DNA was prepared from the peripheral blood of Indian WD patients. PCR was done to amplify
the exons and flanking regions of the WD gene followed by sequencing, to identify the nucleotide variants. Results In addition to previous reports, we recently identified eight mutations including three novel (c.3412 + 1G > A, c.1771 G > A,
c.3091 A > G) variants, and identified patients with variable phenotype despite similar mutation background suggesting potential
role of modifier locus. Conclusions So far we have identified 17 mutations in eastern India including five common mutations that account for 44% of patients.
Comparative study on WD mutations between different regions of India suggests high genetic heterogeneity and the absence of
a single or a limited number of common founder mutations. Genotype–phenotype correlation revealed that no particular phenotype
could be assigned to a particular mutation and even same set of mutations in different patients showed different phenotypes. 相似文献
93.
Human eosinophil-derived neurotoxin (EDN) or RNase 2, found in the non-core matrix of eosinophils is a ribonuclease belonging
to the Ribonuclease A superfamily. EDN manifests a number of bioactions including neurotoxic and antiviral activities, which
are dependent on its ribonuclease activity. The core of the catalytic site of EDN contains various base and phosphate-binding
subsites. Unlike many members of the RNase A superfamily, EDN contains an additional non-catalytic phosphate-binding subsite,
P−1. Although RNase A also contains a P−1 subsite, the composition of the site in EDN and RNase A is different. In the current study we have generated site-specific
mutants to study the role of P−1 subsite residues Arg36, Asn39, and Gln40 of EDN in its catalytic activity. The individual mutation of Arg36, Asn 39, and Gln40 resulted in a reduction in the catalytic activity of EDN on poly(U) and poly(C). However, there was no change in the activities
on yeast tRNA and dinucleotide substrates. The study shows that the P−1 subsite is crucial for the ribonucleolytic activity of EDN on polymeric RNA substrates.
Deepa Sikriwal and Divya Seth contributed equally to this work. 相似文献
94.
The reactions of N,N-dimethylaminopropyl chalcogenolates with platinum(II) compounds have been carried out and complexes of the types [PtCl(ECH2CH2CH2NMe2)]2 (1) (E = S (1a) and Se (1b)), [Pt(ECH2CH2CH2NMe2)2]n (2) (E = S (2a) and Se (2b)), [(PtCl2)2{(Me2NCH2CH2CH2E)2}]n (3), [PtX(SeCH2CH2CH2NMe2)]2 (4) (X = SePh (4a) and OAc (4b)) and [PtCl(ECH2CH2CH2NMe2)(PR3)]n (5) (E = S, Se, Te) have been isolated. These complexes have been characterized by elemental analysis, IR, UV-Vis, NMR (1H, 13C, 31P, 77Se, 195Pt) spectroscopy and FAB mass spectral data. The structures of [PtCl(SeCH2CH2CH2NMe2)]2 (1b) and [PtCl(SCH2CH2CH2NMe2)(PPr3)]2 (5a) have been established by single crystal X-ray diffraction data. Both the molecules have dimeric structures. In 1b, two platinum atoms are held together by symmetrically bridging Se atoms of the chelating selenolate groups. In 5a, two thiolates form a four-membered Pt2S2 bridge with dangling NMe2 groups. 相似文献
95.
The trinuclear complex [L2Cu3(CF3CO2)4] (1) has been synthesized and its crystal structure determined. It consists of a linear arrangement of Cu(II) centers. The central copper atom is bonded to six oxygen atoms and has a tetragonally distorted octahedral geometry, while the terminal copper atoms are bonded to three oxygen and two nitrogen atoms and show a distorted square pyramidal geometry. The complex shows di-μ(O,O′) syn-syn carboxylate bridging as well as monoatomic (μ-O) bridging, along with phenolate (μ-O) oxygen bridging. Cryomagnetic investigations in the range 2-300 K revealed an antiferromagnetic spin exchange interaction with J = −95.7 cm−1, based on the isotropic exchange model Hex = −2J[S1 · S2 + S2 · S3]. 相似文献
96.
Expression of cytokeratin 20 in urine cytology smears: a potential marker for the detection of urothelial carcinoma 总被引:1,自引:0,他引:1
A. Bhatia P. Dey Y. Kumar U. Gautam N. Kakkar R. Srinivasan R. Nijhawan 《Cytopathology》2007,18(2):84-86
BACKGROUND: Urine cytomorphology is one of the oldest methods for screening and monitoring patients with transitional cell carcinoma (TCC). Sensitivity of urine cytology is relatively low. Ancillary techniques on urine sample may increase the sensitivity. AIM: To explore the utility of cytokeratin 20 (CK20) immunostaining in identifying malignant cells in urine cytology smears. MATERIALS AND METHODS: Fourteen cases each of confirmed TCC and benign urinary cytology along with five cases of atypical cells in urine were immunostained with a monoclonal CK20 antibody. Of 14 cases of TCC, 12 showed strong positive staining with the antibody. All benign cases were negative except for a few cases in which the umbrella cells were weakly to moderately positive. In all five cases of atypical urine cytology the atypical cells stained positive with the antibody. These cases were later confirmed as TCC on histopathology of bladder wall biopsy. CONCLUSION: CK20 is an important biomarker that can be used to identify TCC in urine cytology smears. It is particularly useful in those cases where malignancy cannot be confirmed by morphology alone. 相似文献
97.
Banerjee R Sreetama S Saravanan KS Dey SN Mohanakumar KP 《Neurochemical research》2007,32(7):1238-1247
The potent parkinsonian neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is known to cause dopaminergic neurodegeneration
in nigrostriatal system. In the present study we investigated the nuclear morphology of cells in the substantia nigra pars
compacta (SNpc) region of rats following unilateral intranigral infusion of the active metabolite, 1-methyl-4-phenyl pyridinium
ion (MPP+), which resulted in a dose-dependent and prolonged dopamine depletion in the ipsilateral striatum. There appeared a substantial
loss of tyrosine hydroxylase immunoreactive neurons in the SNpc that received the neurotoxin. Specific nuclear staining with
Hoechst 33342 or acridine orange revealed bright pyknotic, shrunken, distorted nuclei and condensed chromatin with perinuclear
nucleolus respectively following visualization with the former and latter dyes in the ipsilateral SNpc, as compared to the
round, intact nuclei and centrally positioned nucleolus in the contralateral side. Ultrastructural details of the nucleus
under transmission electron microscope confirmed distorted nuclear organization with shrunken or condensed nuclei and disrupted
nuclear membrane. These features are typical of nucleus undergoing apoptosis, and suggest that MPP+ causes dopaminergic neuronal death through an apoptotic mode. Typical laddering pattern of genomic DNA isolated from the
ipsilateral SN in agarose gel electrophoresis conclusively established apoptosis following intranigral administration of MPP+ in rats.
Rebecca Banerjee and Sen Sreetama contributed equally to this paper. 相似文献
98.
Lamba A Dey P Kumari S Marwaha N 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2007,29(6):370-376
OBJECTIVE: To study the correlation of histomorphometric data of bone marrow trephine biopsies at the time of initial diagnosis in chronic myeloid leukemia (CML) patients with the patient prognosis. STUDY DESIGN: A total of 40 CML patients were divided equally in group I (developed accelerated phase or blast crisis within 18 months of initial diagnosis of chronic phase of CML) and group II (developed accelerated phase or blast crisis > 30 months after initial diagnosis of chronic phase of CML). The clinical, hematologic and histomorphometric data were compared in the 2 groups of CML patients. RESULTS: The percentage of bone marrow promyelocytes was significantly increased in group I. On morphometry, the number of blasts per square millimeter, the area of reticulin fibers per square millimeter and the percentage area occupied by reticulin fibers were statistically significant. CONCLUSION: There seems to be grounds for hope for predicting prognosis of CML patients at initial diagnosis based on histomorphometric findings. The percentage area of reticulin fibers and the number of blasts per square millimeter are important prognostic predictors in histomorphometry data. 相似文献
99.
Generation of an indexed, saturated, insertional-mutant library is an aid to understanding the functions of genes in an organism. However, 10 years of work by many investigators have not yet yielded such a library in rice. The major reason is that determining the chromosomal locations of a very large number of random insertion mutants by flanking sequence analysis is highly labor intensive, and therefore, libraries that do exist have not been indexed. We report here an efficient procedure to construct an indexed, region-specific, insertional-mutant library of rice. The procedure makes use of efficient long-PCR-based high-throughput indexing, coupled with a random but anchored population of Ds transposants. Long-PCR indexing allows rapid and simultaneous determination of the chromosomal locations of a large number of mutants that surround a particular anchor line, thus converting a random library into an indexed one. Such a library can be used directly, without the need to screen a large random library for a desired mutant plant. 相似文献
100.